10 Breakthrough Technologies 2020 – MIT Technology Review

Here is our annual list of technological advances that we believe will make a real difference in solving important problems. How do we pick? We avoid the one-off tricks, the overhyped new gadgets. Instead we look for those breakthroughs that will truly change how we live and work.

This story is part of our March/April 2020 Issue

Were excited to announce that with this years list were also launching our very first editorial podcast, Deep Tech, which will explore the the people, places, and ideas featured in our most ambitious journalism. Have a listen here.

Later this year, Dutch researchers will complete a quantum internet between Delft and the Hague.

Yoshi Sodeoka

An internet based on quantum physics will soon enable inherently secure communication. A team led by Stephanie Wehner, at Delft University of Technology, is building a network connecting four cities in the Netherlands entirely by means of quantum technology. Messages sent over this network will be unhackable.

In the last few years, scientists have learned to transmit pairs of photons across fiber-optic cables in a way that absolutely protects the information encoded in them. A team in China used a form of the technology to construct a 2,000-kilometer network backbone between Beijing and Shanghaibut that project relies partly on classical components that periodically break the quantum link before establishing a new one, introducing the risk of hacking.

The Delft network, in contrast, will be the first to transmit information between cities using quantum techniques from end to end.

The technology relies on a quantum behavior of atomic particles called entanglement. Entangled photons cant be covertly read without disrupting their content.

But entangled particles are difficult to create, and harder still to transmit over long distances. Wehners team has demonstrated it can send them more than 1.5 kilometers (0.93 miles), and they are confident they can set up a quantum link between Delft and the Hague by around the end of this year. Ensuring an unbroken connection over greater distances will require quantum repeaters that extend the network.

Such repeaters are currently in design at Delft and elsewhere. The first should be completed in the next five to six years, says Wehner, with a global quantum network following by the end of the decade.

Russ Juskalian

Novel drugs are being designed to treatunique genetic mutations.

Julia Dufoss

Heres a definition of a hopeless case: a child with a fatal disease so exceedingly rare that not only is there no treatment, theres not even anyone in a lab coat studying it. Too rare to care, goes the saying.

Thats about to change, thanks to new classes of drugs that can be tailored to a persons genes. If an extremely rare disease is caused by a specific DNA mistakeas several thousand aretheres now at least a fighting chance for a genetic fix.

One such case is that of Mila Makovec, a little girl suffering from a devastating illness caused by a unique genetic mutation, who got a drug manufactured just for her. Her case made the New England Journal of Medicine in October, after doctors moved from a readout of her genetic error to a treatment in just a year. They called the drug milasen, after her.

The treatment hasnt cured Mila. But it seems to have stabilized her condition: it has reduced her seizures, and she has begun to stand and walk with assistance.

Milas treatment was possible because creating a gene medicine has never been faster or had a better chance of working. The new medicines might take the form of gene replacement, gene editing, or antisense (the type Mila received), a sort of molecular eraser, which erases or fixes erroneous genetic messages. What the treatments have in common is that they can be programmed, in digital fashion and with digital speed, to correct or compensate for inherited diseases, letter for DNA letter.

How many stories like Milas are there? So far, just a handful.

But more are on the way. Where researchers would have once seen obstacles and said Im sorry, they now see solutions in DNA and think maybe they can help.

The real challenge for n-of-1 treatments (a reference to the number of people who get the drug) is that they defy just about every accepted notion of how pharmaceuticals should be developed, tested, and sold. Who will pay for these drugs when they help one person, but still take large teams to design and manufacture?

Antonio Regalado

The rise of digitalcurrency has massive ramifications forfinancial privacy.

Last June Facebook unveiled a global digital currency called Libra. The idea triggered a backlash and Libra may never launch, at least not in the way it was originally envisioned. But its still made a difference: just days after Facebooks announcement, an official from the Peoples Bank of China implied that it would speed the development of its own digital currency in response. Now China is poised to become the first major economy to issue a digital version of its money, which it intends as a replacement for physical cash.

Chinas leaders apparently see Libra, meant to be backed by a reserve that will be mostly US dollars, as a threat: it could reinforce Americas disproportionate power over the global financial system, which stems from the dollars role as the worlds de facto reserve currency. Some suspect China intends to promote its digital renminbi internationally.

Now Facebooks Libra pitch has become geopolitical. In October, CEO Mark Zuckerberg promised Congress that Libra will extend Americas financial leadership as well as our democratic values and oversight around the world. The digital money wars have begun.

Mike Orcutt

Drugs that try to treat ailments bytargeting a natural aging process in the body have shown promise.

Yoshi Sodeoka

The first wave of a new class of anti-aging drugs have begun human testing. These drugs wont let you live longer (yet) but aim to treat specific ailments by slowing or reversing a fundamental process of aging.

The drugs are called senolyticsthey work by removing certain cells that accumulate as we age. Known as senescent cells, they can create low-level inflammation that suppresses normal mechanisms of cellular repair and creates a toxic environment for neighboring cells.

In June, San Franciscobased Unity Biotechnology reported initial results in patients with mild to severe osteoarthritis of the knee. Results from a larger clinical trial are expected in the second half of 2020. The company is also developing similar drugs to treat age-related diseases of the eyes and lungs, among other conditions.

Senolytics are now in human tests, along with a number of other promising approaches targeting the biological processes that lie at the root of aging and various diseases.

A company called Alkahest injects patients with components found in young peoples blood and says it hopes to halt cognitive and functional decline in patients suffering from mild to moderate Alzheimers disease. The company also has drugs for Parkinsons and dementia in human testing.

And in December, researchers at Drexel University College of Medicine even tried to see if a cream including the immune-suppressing drug rapamycin could slow aging in human skin.

The tests reflect researchers expanding efforts to learn if the many diseases associated with getting oldersuch as heart diseases, arthritis, cancer, and dementiacan be hacked to delay their onset.

Adam Piore

Scientists have used AI to discover promising drug-like compounds.

The universe of molecules that could be turned into potentially life-saving drugs is mind-boggling in size: researchers estimate the number at around 1060. Thats more than all the atoms in the solar system, offering virtually unlimited chemical possibilitiesif only chemists could find the worthwhile ones.

Now machine-learning tools can explore large databases of existing molecules and their properties, using the information to generate new possibilities. This could make it faster and cheaper to discover new drug candidates.

In September, a team of researchers at Hong Kongbased Insilico Medicine and the University of Toronto took a convincing step toward showing that the strategy works by synthesizing several drug candidates found by AI algorithms.

Using techniques like deep learning and generative models similar to the ones that allowed a computer to beat the world champion at the ancient game of Go, the researchers identified some 30,000 novel molecules with desirable properties. They selected six to synthesize and test. One was particularly active and proved promising in animal tests.

Chemists in drug discovery often dream up new moleculesan art honed by years of experience and, among the best drug hunters, by a keen intuition. Now these scientists have a new tool to expand their imaginations.

David Rotman

We can now affordably build, launch, and operate tens of thousands of satellites in orbit at once.

Julia Dufoss

Satellites that can beam a broadband connection to internet terminals. As long as these terminals have a clear view of the sky, they can deliver internet to any nearby devices. SpaceX alone wants to send more than 4.5 times more satellites into orbit this decade than humans have ever launched since Sputnik.

These mega-constellations are feasible because we have learned how to build smaller satellites and launch them more cheaply. During the space shuttle era, launching a satellite into space cost roughly $24,800 per pound. A small communications satellite that weighed four tons cost nearly $200 million to fly up.

Today a SpaceX Starlink satellite weighs about 500 pounds (227 kilograms). Reusable architecture and cheaper manufacturing mean we can strap dozens of them onto rockets to greatly lower the cost; a SpaceX Falcon 9 launch today costs about $1,240 per pound.

The first 120 Starlink satellites went up last year, and the company planned to launch batches of 60 every two weeks starting in January 2020. OneWeb will launch over 30 satellites later this year. We could soon see thousands of satellites working in tandem to supply internet access for even the poorest and most remote populations on the planet.

But thats only if things work out. Some researchers are livid because they fear these objects will disrupt astronomy research. Worse is the prospect of a collision that could cascade into a catastrophe of millions of pieces of space debris, making satellite services and future space exploration next to impossible. Starlinks near-miss with an ESA weather satellite in September was a jolting reminder that the world is woefully unprepared to manage this much orbital traffic. What happens with these mega-constellations this decade will define the future of orbital space.

Neel V. Patel

Google has provided the first clear proof of a quantum computer outperforming a classical one.

Yoshi Sodeoka

Quantum computers store and process data in a way completely differently from the ones were all used to. In theory, they could tackle certain classes of problems that even the most powerful classical supercomputer imaginable would take millennia to solve, like breaking todays cryptographic codes or simulating the precise behavior of molecules to help discover new drugs and materials.

There have been working quantum computers for several years, but its only under certain conditions that they outperform classical ones, and in October Google claimed the first such demonstration of quantum supremacy. A computer with 53 qubitsthe basic unit of quantum computationdid a calculation in a little over three minutes that, by Googles reckoning, would have taken the worlds biggest supercomputer 10,000 years, or 1.5 billion times as long. IBM challenged Googles claim, saying the speedup would be a thousandfold at best; even so, it was a milestone, and each additional qubit will make the computer twice as fast.

However, Googles demo was strictly a proof of conceptthe equivalent of doing random sums on a calculator and showing that the answers are right. The goal now is to build machines with enough qubits to solve useful problems. This is a formidable challenge: the more qubits you have, the harder it is to maintain their delicate quantum state. Googles engineers believe the approach theyre using can get them to somewhere between 100 and 1,000 qubits, which may be enough to do something usefulbut nobody is quite sure what.

And beyond that? Machines that can crack todays cryptography will require millions of qubits; it will probably take decades to get there. But one that can model molecules should be easier to build.

Gideon Lichfield

We can now run powerful AI algorithms on our phones.

Julia Dufoss

AI has a problem: in the quest to build more powerful algorithms, researchers are using ever greater amounts of data and computing power, and relying on centralized cloud services. This not only generates alarming amounts of carbon emissions but also limits the speed and privacy of AI applications.

But a countertrend of tiny AI is changing that. Tech giants and academic researchers are working on new algorithms to shrink existing deep-learning models without losing their capabilities. Meanwhile, an emerging generation of specialized AI chips promises to pack more computational power into tighter physical spaces, and train and run AI on far less energy.

These advances are just starting to become available to consumers. Last May, Google announced that it can now run Google Assistant on users phones without sending requests to a remote server. As of iOS 13, Apple runs Siris speech recognition capabilities and its QuickType keyboard locally on the iPhone. IBM and Amazon now also offer developer platforms for making and deploying tiny AI.

All this could bring about many benefits. Existing services like voice assistants, autocorrect, and digital cameras will get better and faster without having to ping the cloud every time they need access to a deep-learning model. Tiny AI will also make new applications possible, like mobile-based medical-image analysis or self-driving cars with faster reaction times. Finally, localized AI is better for privacy, since your data no longer needs to leave your device to improve a service or a feature.

But as the benefits of AI become distributed, so will all its challenges. It could become harder to combat surveillance systems or deepfake videos, for example, and discriminatory algorithms could also proliferate. Researchers, engineers, and policymakers need to work together now to develop technical and policy checks on these potential harms.

Karen Hao

A technique to measure the privacy of a crucial data set.

In 2020, the US government has a big task: collect data on the countrys 330 million residents while keeping their identities private. The data is released in statistical tables that policymakers and academics analyze when writing legislation or conducting research. By law, the Census Bureau must make sure that it cant lead back to any individuals.

But there are tricks to de-anonymize individuals, especially if the census data is combined with other public statistics.

So the Census Bureau injects inaccuracies, or noise, into the data. It might make some people younger and others older, or label some white people as black and vice versa, while keeping the totals of each age or ethnic group the same. The more noise you inject, the harder de-anonymization becomes.

Differential privacy is a mathematical technique that makes this process rigorous by measuring how much privacy increases when noise is added. The method is already used by Apple and Facebook to collect aggregate data without identifying particular users.

But too much noise can render the data useless. One analysis showed that a differentially private version of the 2010 Census included households that supposedly had 90 people.

If all goes well, the method will likely be used by other federal agencies. Countries like Canada and the UK are watching too.

Angela Chen

Researchers can now spot climate changes role in extreme weather.

Yoshi Sodeoka

Ten days after Tropical Storm Imelda began flooding neighborhoods across the Houston area last September, a rapid-response research team announced that climate change almost certainly played a role.

The group, World Weather Attribution, had compared high-resolution computer simulations of worlds where climate change did and didnt occur. In the former, the world we live in, the severe storm was as much as 2.6 times more likelyand up to 28% more intense.

Earlier this decade, scientists were reluctant to link any specific event to climate change. But many more extreme-weather attribution studies have been done in the last few years, and rapidly improving tools and techniques have made them more reliable and convincing.

This has been made possible by a combination of advances. For one, the lengthening record of detailed satellite data is helping us understand natural systems. Also, increased computing power means scientists can create higher-resolution simulations and conduct many more virtual experiments.

These and other improvements have allowed scientists to state with increasing statistical certainty that yes, global warming is often fueling more dangerous weather events.

By disentangling the role of climate change from other factors, the studies are telling us what kinds of risks we need to prepare for, including how much flooding to expect and how severe heat waves will get as global warming becomes worse. If we choose to listen, they can help us understand how to rebuild our cities and infrastructure for a climate-changed world.

James Temple

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10 Breakthrough Technologies 2020 - MIT Technology Review

Research finds majority of people with cystic fibrosis can be treated successfully with three-drug combo – BreakingNews.ie

Groundbreaking research has found that the majority of people with cystic fibrosis can be treated successfully.

Researchers at Queens University in Belfast and at the Cystic Fibrosis Unit at St Vincents Hospital Dublin, have identified how a combination of three drugs, known as triple therapy, can tackle the underlying cause of the incurable disease.

The drug, Trikaftatm, targets the root cause of cystic fibrosis (CF), a genetic condition that clogs up the lungs and digestive system, making breathing difficult and often resulting in an early death for those affected.

CF is an inherited chronic disease that primarily affects the lungs and digestive system of about 1,300 children and adults in Ireland and 70,000 worldwide.

That figure, according to Philip Watt of Cystic Fibrosis Ireland, is set to increase by 75% in adults and 25% in children in this country according to ongoing studies by 2025.

This new drug Trikaftatm will benefit 90% of sufferers worldwide, lung function is expected to increase dramatically and will result in a 60% decrease in hospitalisation. This is a hugely welcome advancement. Many of the trials by the Queens University researchers were carried out at several centres in Ireland including St Vincents Hospital Dublin.

Dr Francis Collins, an American researcher who discovered the CF gene in 1989 has already said this is the breakthrough in research he has been waiting for. Many of the trials prior to this did not achieve as much as this study has.

Dr Collins who is the director of the National Institutes of Health writing in The New England Journal of Medicine and the highly respected Lancet medical magazine over the weekend, said these findings indicate that it may soon be possible to offer safe and effective molecularly targeted therapies to 90% of persons with cystic fibrosis.

He said that this should be a cause for major celebration and the best day ever for all of us traveling down this long road together will be the day when the more than 70,000 persons with cystic fibrosis worldwide do not need to take drug therapy at all and there finally is a permanent cure for cystic fibrosis that works for everyone.

Mr Watt added: The Food and Drugs Administration in the US has approved this drug five months ahead of time and now the European Medicines Agency is reviewing it. As a result we would expect this drug to be on the market here by the Summer of next year to those over 12-years-of-age. We would be hopeful that will include children aged as young as two in the future.

The numbers of adults and children increasing in Western Europe is down to advancements in related drugs and quality of services.

Talks and negotiations with the Health Service Executive on this new announcement will, Im sure, commence as a pipeline deal on future drug advancements was agreed with them in 2017 when Orkambi was finally approved. So far we are not privy to the potential costs of this new drug.

However, it is estimated that the drug may cost around $311,000 or 279,000 annually by Vertex, a pharmaceutical company that produces other CF drugs.

Ireland has the highest incidence of CF in the world with one in 19 Irish people being said to carry one copy of the altered gene, with three times the rate of the United States and the rest of the EU.

The organisation has pointed out that it is important to have a network of centres of expertise in dealing with disease.

A defective gene and its protein product cause the body to produce unusually thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections; and obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.

Researchers believe it is possible to help control the symptoms and delay complications to make the condition easier to live with.

Dr Damian Downey, is a Clinical Senior Lecturer at the Wellcome-Wolfson Institute for Experimental Medicine, Queens University Belfast and co-author on the worldwide trial, set-up to assess the safety and efficacy of a new triple-drug combination called Trikaftatm in patients with CF aged 12 years and older.

The study involved a four-week, randomised, active-controlled trial in 107 patients who had two copies of the (F508del) most common gene mutation.

Dr Downey said: The trial was a success in demonstrating that this drug combination can potentially treat up to 90% of people with CF by addressing the underlying cause of their disease.

This new triple therapy has the potential to transform the lives of people with CF. It results in a significant improvement in lung function and quality of life and also reduces the frequency of chest infections. This treatment will likely alter the future of CF care.

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Research finds majority of people with cystic fibrosis can be treated successfully with three-drug combo - BreakingNews.ie

Genialis and Oncologie Collaborate on Precision Medicine Initiative in Gastric Cancer – Business Wire

SAN RAMON, Calif. & WALTHAM, Mass.--(BUSINESS WIRE)--Genialis, a leader in applied data science for the development of precision medicines, today announced a collaborative partnership with Oncologie, an international, clinical-stage biopharma developing next-generation immunotherapies for cancer. Initial activities will focus on the use of Genialis Expressions software platform and analytics IP with Oncologies clinical and translational expertise to refine patient stratification methodologies.

We are incredibly excited to work with Genialis on this cutting-edge, precision medicine project. To be able to better understand the patients tumor microenvironment phenotype and how it is related to patient benefit represents a key objective for the future success of our company, says Oncologie CEO Laura Benjamin.

Early work between the two companies has thus far focused on modeling gene expression signatures predictive of treatment for gastric cancer. The patent-pending enhanced methodology will further Oncologies clinical development plans to expand beyond gastric cancer to other tumor microenvironment phenotypes.

One of the most encouraging trends in drug development is innovation around integrating and interrogating diverse datasets. Data from historical literature, public population studies, first in human trials, et cetera, can be leveraged to answer significant questions on how to make safe and effective treatments more readily available to patients fighting debilitating and deadly diseases, says Genialis CEO Rafael Rosengarten. Our work in data science requires a great deal of artistry in addition to technology. And benefits from hand-in-hand collaboration with biology domain experts, which makes this opportunity with Oncologie so special. Right from the start, we knew we shared a vision and a commitment to the process.

This week Genialis will present its work on predictive models for patient stratification at the Precision Medicine World Conference in Santa Clara, CA on January 22.

About Oncologie, Inc.

Oncologie, Inc. is an innovative biopharmaceutical company committed to delivering better outcomes for cancer patients through improved approaches to patient selection and clinical trial design. Our current pipeline includes clinical programs that improve treatment outcomes by modulating the tumor micro-environment and enhancing the immune response to targeting cancer cells. From its headquarters in Boston, Massachusetts and Shanghai, China, Oncologie is working with global partners to acquire and develop innovative drugs for cancer patients around the world. For more information on Oncologie, Inc., please visit http://www.oncologie.international.

About Genialis

Genialis is a data science and drug discovery company focused on new ways to treat disease. Blending computational biology and AI-based methods, Genialis merges and models data at the intersection of clinical and translational medicine. Genialis is trusted by biopharma and big pharma alike, to identify targets, predict biomarkers and optimally position novel drugs. Together, Genialis and its partners work to bring improved solutions to drug discovery to change people's lives.

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Genialis and Oncologie Collaborate on Precision Medicine Initiative in Gastric Cancer - Business Wire

Surprises in Cell Codes Reveal Information Goes Far Beyond DNA – Discovery Institute

Information is the stuff of life. Not limited to DNA, information is found in most biomolecules in living cells. Here are some recent developments.

Certain forms of sugars (polysaccharides called chitosans) trigger the immune system of plants. Biologists at the University of Mnster are deciphering the sugar code. They describe the variables in chitosans that constitute a signaling system.

Chitosans consist of chains of different lengths of a simple sugar called glucosamine. Some of these sugar molecules carry an acetic acid molecule, others do not. Chitosans therefore differ in three factors: the chain length and the number and distribution of acetic acid residues along the sugar chain. For about twenty years, chemists have been able to produce chitosans of different chain lengths and with different amounts of acetic acid residues, and biologists have then investigated their biological activities. [Emphasis added.]

These polysaccharides, also found in animals, are perhaps the most versatile and functioning biopolymers, the scientists say. If they can learn to decipher this complex code, they might find ways to protect plants without the use of pesticides.

DNA is becoming known as a more of a team member in a society of biomolecules. In some ways, it is more a patient than a doctor. It gets operated on by numerous machines that alter its message. One of the most important doctors that operates on RNA transcripts is the spliceosome, says a review article in The Scientist about alternative splicing. This complex molecular machine can multiply the messages in the coding regions of DNA by cutting out introns and stitching coded parts called exons together in different ways.

The process of alternative splicing, which had first been observed 26 years before the Human Genome Project was finished, allows a cell to generate different RNAs, and ultimately different proteins, from the same gene. Since its discovery, it has become clear that alternative splicing is common and that the phenomenon helps explain how limited numbers of genes can encode organisms of staggering complexity. While fewer than 40 percent of the genes in a fruit fly undergo alternative splicing, more than 90 percent of genes are alternatively spliced in humans.

Astoundingly, some genes can be alternatively spliced to generate up to 38,000 different transcript isoforms, and each of the proteins they produce has a unique function.

The discovery of splicing seemed bizarre from an evolutionary perspective, the authors say, recalling obsolete ideas about junk DNA. It seemed weird and wasteful that introns were being cut out of transcripts by the spliceosome. Then, the ENCODE project found that the vast majority of non-coding DNA was transcribed, giving these seemingly nonfunctional elements an essential role in gene expression, as evidence emerged over the next few years that there are sequences housed within introns that can help or hinder splicing activity.

This article is a good reminder that evolutionary assumptions hinder science. Once biochemists ridded themselves of the evolutionary notion of leftover junk in the genetic code, a race was on to understand the role of alternative splicing.

Understanding the story behind each protein in our bodies has turned out to be far more complex than reading our DNA. Although the basic splicing mechanism was uncovered more than 40 years ago, working out the interplay between splicing and physiology continues to fascinate us. We hope that advanced knowledge of how alternative splicing is regulated and the functional role of each protein isoform during development and disease will lay the groundwork for the success of future translational therapies.

Another discovery that is opening doors to research opportunities comes from the University of Chicago. Darwin-free, they announce a fundamental pathway likely to open up completely new directions of research and inquiry. Biologists knew about how methyl tags on RNA transcripts regulate the ways they are translated. Now, Professor Chuan He and colleagues have found that some RNAs, dubbed carRNAs, dont get translated at all. Instead, they controlled how DNA itself was stored and transcribed.

This has major implications in basic biology, He said. It directly affects gene transcriptions, and not just a few of them. It could induce global chromatin change and affects transcription of 6,000 genes in the cell line we studied.

Dr. He is excited about the breakthrough. The conceptual change in how RNA regulates DNA offers an enormous opportunity to guide medical treatments and promote health. Take a look at this design-friendly quote:

The human body is among the most complex pieces of machinery to exist. Every time you so much as scratch your nose, youre using more intricate engineering than any rocket ship or supercomputer ever designed. Its taken us centuries to deconstruct how this works, and each time someone discovers a new mechanism, a few more mysteries of human health make sense and new treatments become available.

Remember the evolutionary myth that jumping genes were parasites from our evolutionary past that learned how to evade the immune system? A discovery at the Washington University School of Medicine changes that tune, saying, Jumping genes help stabilize DNA folding patterns. These long-misunderstood genes thought by some evolutionists to be sources of novel genetic traits actually function to provide genomic stability.

Jumping genes bits of DNA that can move from one spot in the genome to another are well-known for increasing genetic diversity over the long course of evolution. Now, new research at Washington University School of Medicine in St. Louis indicates that such genes, also called transposable elements, play another, more surprising role: stabilizing the 3D folding patterns of the DNA molecule inside the cells nucleus.

It appears that by moving around, these genes can preserve the structure of DNA while not altering its function. (Note: the evolution they speak of appears to be microevolution, which is not controversial; hear Jonathan Wells discuss this on ID the Future.)

According to the researchers, this redundancy makes the genome more resilient. In providing both novelty and stability, jumping genes may help the mammalian genome strike a vital balance allowing animals the flexibility to adapt to a changing climate, for example, while preserving biological functions required for life.

Lead author Ting Wang says this gives insight into why coding regions between different animals vary in structure.

Our study changes how we interpret genetic variation in the noncoding regions of the DNA, Wang said. For example, large surveys of genomes from many people have identified a lot of variations in noncoding regions that dont seem to have any effect on gene regulation, which has been puzzling. But it makes more sense in light of our new understanding of transposable elements while the local sequence can change, but the function stays the same.

So while evolutionists had expected junk and simplicity, Wang says the opposite has occurred. We have uncovered another layer of complexity in the genome sequence that was not known before. Now, more discoveries are likely to flow from intelligent designs expectation that a closer look reveals more complexity.

In another recent podcast at ID the Future honoring the late Phillip E. Johnson, Paul Nelson likened a graph of mounting discoveries about life to a sharply rising mountain range. Darwin proposed his theory on the flatlands, unaware of the peaks his theory would have to explain. In the last fifty years, scientists have encountered mountain after mountain of complexity in life that evolutionary theory never anticipated back out there on the flatlands. We cant see the top of the mountains yet, but we know that were still not there, and we wont be for a long, long time, Nelson says. As we witness scientists continuing up the mountains, we anticipate with awe more wonders of design that will likely come to light in the next decade.

Image: Interior of a cell, courtesy of Illustra Media.

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Surprises in Cell Codes Reveal Information Goes Far Beyond DNA - Discovery Institute

‘Beating Heart in a Box’ Promises Major Revolution in Medical Care – NBCNews.com

Jun.09.2017 / 11:36 AM ET

A lot has changed in medicine since the first human organ a kidney was successfully transplanted into another human in 1954. But one part of the transplant process that hasn't changed much since then is how the organ is delivered from donor to recipient. Basically, organs still travel via cooler.

An organ is first removed from the donor and flushed with a salty preservative solution. Its then put on ice and sent to a hospital where the recipient is waiting.

The technology thats currently widely in use has really been in place for close to 50 years now, says Dr. David Klassen, chief medical officer of the United Network for Organ Sharing, the private non-profit that manages the organ transplant system in the United States.

But that standard is about to change. New devices make it possible to keep donor organs in a functioning state at body temperature while theyre being transported.

The devices can monitor an organs health more closely before its transplanted, which means doctors can better predict whether an organ will function properly in its new host. The device uses a technology called ex vivo warm perfusion that allows donated organs to stay outside of a human body for longer periods of time, so they can be sent farther distances to waiting recipients.

The time constraints imposed by organ preservation are a fundamental limitation in the current organ allocation system, Klassen says.

Related: Self-Driving Cars Will Create an Organ Shortage Can Science Meet the Demand?

Organs start to deteriorate as soon as theyre removed so when theyre shipped cold, after a certain amount of time they are no longer viable. Kidneys can last up to 36 hours on ice, but hearts and lungs can only be kept out of the body for about four to six hours.

You typically cannot send a heart from Los Angeles to New York, Klassen says.

Warm perfusion will allow for significantly more donated organs to be delivered in time for a transplant, he explains. The system will be more successful, fair, and efficient.

The devices are already being used in Europe, Canada, Australia, and elsewhere for kidney, heart, lung, and liver transplants. And TransMedics' Organ Care System for lung transplants the first device of this kind is currently up for FDA approval in the U.S.

The Organ Care System the so-called beating heart in a box works by pumping a donor organ with warm, oxygenated, and nutrient-enriched blood. The carbon fiber system is about waist-high and the whole thing sits on a four-wheeled cart for easy transport. Its equipped with an oxygen tank, supply of blood, batteries, and special electric and mechanical equipment to monitor the organ, as well as a sterile plastic box that houses the donor organ during delivery, keeping it at the right temperature and humidity levels.

The organ believes that its still in the body, says Dr. Waleed Hassanein, president and CEO of TransMedics, the Andover, Mass.-based medical device company thats developing the system. The heart is beating. The lung is breathing. The liver is making bile. The kidneys are making urine.

Because the organs are functioning during transport, doctors can monitor the organs and in some cases make them healthier, Hassanein adds. Antibiotics can be delivered to an organ to prevent or treat an infection. Clinicians can inflate sections of a donor lung that have collapsed.

In the future it may be possible to apply new fields of research, such as gene therapy or regenerative medicine, to actually improve organs before a transplant, Hassanein says. It opens up a huge area of scientific and clinical innovation.

More than 815 successful human organ transplants have been performed using TransMedics perfusion devices so far in other countries. And the company is currently sponsoring five U.S. clinical trials for its devices and is developing a perfusion device for kidney transplants.

The heart is beating. The lung is breathing. The liver is making bile. The kidneys are making urine.

Several international companies, including OrganOx, XVIVO Perfusion, and Organ Assist are making warm organ storage devices abroad. Here in the U.S., Lung Bioengineering in Silver Spring, Md. is developing similar devices. And Revai, a New Haven, Conn.- based company founded by scientists from Yale Universitys School of Medicine and School of Engineering and Applied Sciences, is using warm perfusion technology to develop a transport device for small intestines.

Were seeing this technology transform the entire field as we speak, Hassanein says. Theres not enough data yet to quantify exactly how many more organs these devices will help be transplanted in the near future, but Hassanein suspects it could as much as double or triple the number of successful procedures.

Related: The Quest to Create Artificial Blood May Soon Be Over

UNOS is currently strategizing how to incorporate warm perfusion into its organ allocation systems, Klassen says. The devices that use it are expensive and it will take some time for them to be rolled out, but Klassen expects these devices to be used extensively within the next few years. Its the patients on organ transplant waiting lists that will benefit in big and noticeable ways, he adds

The new devices will allow more organs to be transplanted into recipients who currently often wait many years before receiving a transplant (and some who never do), Klassen says. And its going to allow [transplanted organs] to function better and for longer periods of time.

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'Beating Heart in a Box' Promises Major Revolution in Medical Care - NBCNews.com

Is CRISPR Gene Editing Moving Ahead Too Quickly? – Healthline

Researchers say they discovered hundreds of mutations during a gene editing experiment, casting doubt on CRISPR's safety and precision.

CRISPR gene editing technology has tantalized the public with its potential to cure disease.

However, new research suggests it could be more dangerous and less precise than previously believed.

CRISPR-Cas9 was discovered in 2012 by University of California molecular biologist Jennifer Doudna and her colleagues. It allows for genetic editing by snipping out small bits of defective or harmful DNA and replacing it.

Gene editing has existed since the 1970s, but CRISPR-Cas9 has reinvented it as a precise, accessible technology.

The potential applications seem almost limitless.

This year, Dr. Edze Westra of the University of Exeter, told the Independent that he expects the technology to be used to cure all inherited diseases, to cure cancers, to restore sight to people by transplanting genes.

Read more: Scientists find gene editing with CRISPR hard to resist

Still in its infancy, CRISPR-Cas9 has yet to deliver on these promises, in humans anyway.

One of the key talking points of CRISPR-Cas9 has been its precision its ability to accurately edit small sections of DNA without affecting nearby sections.

However, a new study from Columbia University says that CRISPR-Cas9 can introduce hundreds of unexpected mutations into the genome beyond what was intended.

We feel its critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, said co-author Dr. Stephen Tsang, a professor at Columbia University Medical Center, in a press release.

Tsang and his team discovered the mutations while conducting research on mice, using CRISPR-Cas9 to correct a gene that caused blindness.

The technology worked effectively in curing the blindness, but when the researchers later looked at the genome of the mice, they said they found additional, unintended mutations.

Despite this, the mice appeared to be in fine health.

We did not see any observable complications in the mice, despite having all these extra CRISPR-related mutations, Tsang told Healthline.

Sheila Jasanoff, professor of science and technology studies at Harvard University, told Healthline that precision can have a slippery definition in biotechnology.

Genetic engineering was also sold some 40 years ago as a highly precise technique. Now, CRISPR is being heralded as even more precise, she said.

Undoubtedly, there is some truth in that claim ... But we also know from older genetic engineering techniques that very precise interventions into one part of a genome can produce unexpected side effects or off-target impacts that scientists were not expecting, Jasanoff added.

Read more: CRISPR gene editing and cancer treatment

Tsang frames the message of his research in two ways.

First, he hopes that his work will bring a newfound awareness to the potential side effects caused by CRISPR.

Although the mutations he and his team observed did not appear to have any malignant effects, they should be a wake-up call for researchers.

Secondly, Tsang says that no matter what kind of medicine or treatment is being used, there is the potential for side effects.

If we apply CRISPR, its just like any other intervention medicine. There is always off-targeting and risks and benefits, he says.

Jasanoff is more tempered in her assessment of the risk vs. reward of CRISPR.

The assumption that there are untold benefits in store long before the work has been done to establish how a new technology actually will have an impact on any disease is a typical example of the hype that surrounds new and emerging technologies, she said.

Tsangs research offers no hard answers to the larger questions of efficacy, risk, and benefit of using CRISPR on humans.

Lets not go overboard, said Pete Shanks, a consultant who is an expert on genetics. Three blind mice dont prove much.

Tsangs research does provide some cautionary insight into how research must be conducted in order to make the technology safer.

Currently most studies of off-target mutations depend on computer algorithms to locate and examine affected areas. Tsang and his team say that this isnt sufficient when using live specimens.

These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals, Alexander Bassuk, professor of pediatrics at the University of Iowa, and co-author of the study, said in a press release.

Researchers who arent using whole genome sequencing to find off-target effects may be missing potentially important mutations, Tsang said.

Read more: Gene editing could be used to battle mosquito-borne disease

This study comes at an important time.

China has begun its first round of human testing using CRISPR-Cas9.

The United States is due to start its own tests next year.

The research field is moving quickly perhaps too quickly.

We hope our findings will encourage others to use whole genome sequencing as a method to determine all the off-target effects of their CRISPR techniques and study different versions for the safest, most accurate editing, Tsang said.

Jasanoff is much blunter.

We should put aside the notion the benefits of CRISPR are already proven, and all we need to worry about is risks, she said.

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Is CRISPR Gene Editing Moving Ahead Too Quickly? - Healthline

New study decodes gene function that protects against type 2 diabetes – Health Europa

Type 2 diabetes affects almost 400 million people across the world. Diabetes is caused by a combination of lifestyle as well as genetic factors which together result in high blood sugar levelsOne such genetic factor that can influence blood sugar levels is a variation in a gene called SLC30A8, which encodes a protein which carries zinc.

This protein is important, because zinc is essential for ensuring that insulin, (the only hormone that can reduce blood sugar levels) has the right shape in the beta-cells of the pancreas.

Researchers have known for almost ten years that changes in this gene can reduce the risk of getting type 2 diabetes, but not how this happened. They now recruited new members from families with a rare mutation in the SLC30A8 gene to study how they responded to sugar in a meal.

Departmental chief doctor Tiinamaija Tuomi from the Helsinki University Hospital, who co-led the study, said: A definite strength of our study is we could study families. We could compare people with the mutation with their relatives who do not have the mutation, but who have similar genetic background and life-style.

This way, we could make sure that the effects we were seeing were definitely because of this gene, and not because of another genetic or life-style factor.

The results showed that people with the mutation have higher insulin and lower blood sugar levels, reducing their risk for diabetes.

An international collaboration of 50 researchers also studied pancreatic cells with and without the mutation in the lab and carried out experiments in mice and human cellular material to understand exactly what was happening when the function of the SLC30A8 gene changed.

Professor Anna Gloyn, who co-led the study, from the Wellcome Centre for Human Genetics, University of Oxford, said: The work is a collaborative effort bringing pharma and academia together and researchers from multiple European Countries. It is a tour de force, since we were able to measure the impact of the mutation in many different systems, including human beta-cells.

Dr Benoit Hastoy, co-first author from the Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford said: We found that this mutation had collateral consequences on key functions of pancreatic beta cells and during their development. Importantly, this study exposes the extraordinary molecular complexity behind a specific gene variation conferring risk or protection from type 2 diabetes.

Taken together, the human and model system data show enhanced glucose-stimulated insulin secretion combined with enhanced conversion of the prehormone proinsulin to insulin as the most likely explanation for protection against type 2 diabetes, said Om Prakash Dwidedi, the co- first author of the study from the Institute for Molecular Medicine Finland (FIMM), University of Helsinki.

Better understanding of the genetic and pathological mechanism behind diabetes can open up new ways of preventing or treating type 2 diabetes.

Professor Leif Groop from the University of Helsinki and the Lund University who directed the study, added: Our results position this zinc transporter as an appealing and safe target for antidiabetic therapies. If a drug can be developed that mimics the protective effect of this mutation, beta-cell function could be preserved and the insulin secretion capacity in diabetic patients maintained.

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New study decodes gene function that protects against type 2 diabetes - Health Europa

Enigmatic chemical tag is altered in autism brains – Spectrum

Download PDF DNA decor: Cells dot DNA with molecules to dial down gene expression at those spots.

shunyufan / iStock

An understudied chemical modification that influences gene expression is abundant in the brains of people with autism, according to a new study1. The results are too preliminary to be conclusive, but they point to new avenues of study, experts say.

The modification, or tag, is a methyl group that attaches to the DNA base cytosine. The most-studied form of DNA methylation, called CpG methylation, targets cytosines that are followed by another base, guanine. Some researchers have found atypical patterns of CpG methylation in autism brains.

The new study focuses on nonCpG methylation, in which a methyl group sticks to cytosines followed by a DNA base other than guanine. This type of methylation is found almost exclusively in the brain.

This opens up new avenues of research that perhaps we havent considered carefully before, says lead researcher Dan Arking, associate professor of genetic medicine at Johns Hopkins University in Baltimore, Maryland.

In particular, efforts to study the role of DNA modifications in autism might center on this class of chemical modification, says Hongjun Song, professor of neurology and neuroscience at Johns Hopkins, who was not involved in this study. Theres a lot more cytosines to look at in terms of methylation, Song says, rather than just those followed by a guanine.

The study, which appeared 17 February in Molecular Autism, is the largest of its kind. Researchers presented preliminary results from the work at the 2016 International Meeting for Autism Research in Baltimore.

A body of work implicates methyl groups in autism. Many genes linked to autism reside in regions of the genome with a high density of these tags. And postmortem brain tissue from people with autism has revealed unusually high expression of a gene that helps to remove methyl tags.

Most of these studies focus on CpG sites. In the new study, the researchers used an inexpensive method that enables detection of methyl groups on cytosines next to any DNA base. The method is limited to 1 percent of the genome, however the parts known to have a high density of CpGs.

The researchers found that brain tissue from 29 people with autism has double the number of tagged nonCpG sites as tissue from 34 controls. These sites do not fall within autism genes, but cluster in regulatory regions of the genome.

Some of the excess nonCpG groups fall in so-called beacons regions of the genome that are rich in CpG sites and are present only in people (not in other primates). These regions are thought to underlie traits that are uniquely human.

NonCpG methylation also clustered in repetitive regions of the genome, which are similarlythought to distinguish humans from other primates.

One could imagine that these may be the regions that are more relevant to phenotypes of autism, such as language deficits, Arking says.

The researchers also saw excess methylation in certain histones proteins that package DNA. Histone methylation can make DNA harder to access, suppressing gene expression.

Its unclear what the findings mean for autism research. There is some evidence that nonCpG methylation lowers gene expression, but no one has directly tested this effect, says Eran Mukamel, assistant professor of cognitive science at University of California, San Diego, who was not involved in the study.

What role, if any, it plays in regulating gene expression, we just dont know yet, Mukamel says.

This type of DNA modification is found almost exclusively in neurons, and occurs during a period of development relevant to autism, however.

In a 2013 study, Mukamel and his colleagues found that the pattern of methyl groups in the DNA of neurons changes across the lifespan2. Unlike CpG methylation, which occurs in the embryo, nonCpG methylation begins around birth and increases rapidly during the first two years of life, when neurons are forming their connections.

The timing of the nonCpG accumulation is intriguing, Mukamel says. Its the time window when symptoms of neurodevelopmental disorders like autism start to emerge.

The tissue examined in the study covered a wide age range: 2 to 68 years. Because the density of nonCpG methyl groups changes during development, a difference in methylation among adults would be more convincing, Mukamel says. Whats more, the methylation levels within the autism and control groups vary greatly, weakening the statistical strength of the findings.

Arking and his team are working to confirm their results in additional brain-tissue samples. They are also investigating whether the altered patterns of methyl groups at nonCpG sites contribute to autism or stem from it.

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Enigmatic chemical tag is altered in autism brains - Spectrum

MiMedx To Present At 5th Annual Cell & Gene Therapy Investor Day – PR Newswire (press release)

MARIETTA, Ga., April 18, 2017 /PRNewswire/ -- MiMedx Group, Inc. (NASDAQ: MDXG), the leading biopharmaceutical company developing and marketing regenerative biologics utilizing human placental tissue allografts and patent-protected processes for multiple sectors of healthcare, announced today that Dr. Mark Landy, Vice President Strategic Initiatives, will represent the Company at the 5th Annual Cell & Gene Therapy Investor Day in Boston, Massachusetts. The presentation will be conducted "investor conference" style, with a 5-minute introduction by the presenter, followed by a 10 minute "fireside chat" discussion on stage with a leading research analyst. The MiMedx timeslot is scheduled for Thursday, April 27, at 8:55 a.m. eastern time, at The State Room, Boston, Massachusetts. A webcast of this presentation will be available on the Company's website, http://www.mimedx.com

About ARM's Cell & Gene Therapy Investor DayOrganized by the Alliance for Regenerative Medicine (ARM) and co-hosted with Piper Jaffray, this one-day, high impact program provides institutional, strategic and venture investors with unique insight into the financing hypothesis for advanced therapies-based treatment and tools. The event includes clinical and commercial experts who are on-hand to address specific questions regarding the outlook for these products, as well as offer insight into how cell and gene therapies could impact the standard of care in key therapeutic areas such as cardiovascular disease, wound healing and tissue repair, ophthalmology, neurodegenerative diseases, diabetes and oncology. The program will include talks by key opinion leaders in the industry, life science investment experts and analysts covering the sector as well as presentations by more than 30 leading companies from across the globe.

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MiMedx To Present At 5th Annual Cell & Gene Therapy Investor Day - PR Newswire (press release)

Gene sequencing study reveals unusual mutations in endometriosis – Medical Xpress

May 10, 2017 Endometriosis in the peritoneal tissue (left) forming a scar. Under microscopy, it is composed of glands and surrounding stroma with chronic inflammation and fibrosis. Credit: le-Ming Shih

Using gene sequencing tools, scientists from Johns Hopkins Medicine and the University of British Columbia have found a set of genetic mutations in samples from 24 women with benign endometriosis, a painful disorder marked by the growth of uterine tissue outside of the womb. The findings, described in the May 11 issue of the New England Journal of Medicine, may eventually help scientists develop molecular tests to distinguish between aggressive and clinically "indolent," or non-aggressive, types of endometriosis.

"Our discovery of these mutations is a first step in developing a genetics-based system for classifying endometriosis so that clinicians can sort out which forms of the disorder may need more aggressive treatment and which may not," says Ie-Ming Shih, M.D., Ph.D., the Richard W. TeLinde Distinguished Professor in the Department of Gynecology & Obstetrics at the Johns Hopkins University School of Medicine and co-director of the Breast and Ovarian Cancer Program at the Johns Hopkins Kimmel Cancer Center.

Endometriosis occurs when tissue lining the uterus forms and grows outside of the organ, most often into the abdomen. The disease occurs in up to 10 percent of women before menopause and half of those with abdominal pain and infertility problems. In the 1920s, Johns Hopkins graduate and trained gynecologist John Sampson first coined the term "endometriosis" and proposed the idea that endometriosis resulted when normal endometrial tissue spilled out through the fallopian tubes into the abdominal cavity during menstruation.

The new study, Shih says, challenges that view. The presence of the unusual set of mutations they found in their tissue samples, he says, suggests that while the origins of endometriosis are rooted in normal endometrial cells, acquired mutations changed their fate.

For reasons the researchers say are not yet clear, the mutations they identified have some links to genetic mutations found in some forms of cancer. They emphasize that although abnormal tissue growth in endometriosis often spreads throughout the abdominal cavity, the tissue rarely becomes cancerous except in a few cases when ovaries are involved.

For the study, Shih and his colleagues sequencedor figured out the genetic alphabeta part of the genome known as the exome, which contains all of the genes that can be expressed and make proteins. Specifically, they sequenced the exome of both normal tissue and endometriosis tissue removed during laparoscopic biopsies on 24 women, some with more than one abnormal endometrial growth. All had deep infiltrating endometriosis, the type that typically causes pain and infertility.

Seven of the 24 women were from Japan; the rest were patients at Lenox Hill Hospital-Northwell Health in New York City. The use of samples from Japanese women was selected because endometriosis before menopause occurs more often in Asian women (13-18 percent) than in Caucasian women (6-10 percent), Shih says.

The scientists looked for mutations, or abnormal changes in the DNA, and filtered out normal variations in genes that commonly occur among humans. Of the 24 women, 19 had one or more mutations in their endometriosis tissue that were not present in their normal tissue.

The type and number of mutations varied per endometriosis lesion and between each of the women. The most common mutations, occurring in five of the women, occurred in genes including ARID1A, PIK3CA, KRAS and PPP2R1A, all known for controlling cell growth, cell invasion and DNA damage repair.

Mutations in these genes have been associated with one of the deadliest types of ovarian cancer, called clear cell carcinoma. Nickolas Papadopoulos, Ph.D., professor of oncology and pathology at the Johns Hopkins Kimmel Cancer Center, led the team that completed the first sequencing of the clear cell ovarian cancer genome in 2010.

"We were surprised to find cancer-linked genes in these benign endometriosis samples because these lesions do not typically become cancer," says Papadopoulos, whose Ludwig Center laboratories performed the sequencing. "We don't yet understand why these mutations occur in these tissues, but one possibility is that they could be giving the cells an advantage for growth and spread."

In an additional group of endometriosis samples biopsied from 15 women at the University of British Columbia, the scientists looked specifically for mutations in the KRAS gene, whose expression signals proteins that spur cell growth and replication. They found KRAS mutations in five of the 15 patients.

The scientists make clear that their sequencing studies may have missed mutations in some of the samples. Their data do not at this point reveal the aggressiveness of the lesions.

However, Shih says, he and his team are working on additional studies to determine if the mutations correlate with patients' outcomes. He says a molecular test that sorts lesions as more or less aggressive has the potential to help doctors and patients decide how to treat and monitor the progression and control of the disease. "We may also be able to develop new treatments for endometriosis that use agents that block a gene-related pathway specific to a person's disease," says Shih.

Women with endometriosis are typically prescribed anti-hormonal treatments that block estrogen to shrink lesions. When the disease occurs in the ovaries and forms a large cyst, which increases the risk of developing ovarian cancer, the lesion is usually surgically removed.

Explore further: Gene mutation discovery sparks hope for effective endometriosis screening

Researchers at Yale School of Medicine have, for the first time, described the genetic basis of endometriosis, a condition affecting millions of women that is marked by chronic pelvic pain and infertility. The researchers' ...

(Medical Xpress)Some women with endometriosis, a chronic inflammatory disease, are predisposed to ovarian cancer, and a genetic screening might someday help reveal which women are most at risk, according to a University ...

In the largest genomics study of clear cell endometrial cancer (CCEC) tumors to date, National Human Genome Research Institute (NHGRI) researchers and their collaborators have identified mutations in the TAF1 gene. They've ...

About 5 to 10 percent of the general female population is affected with endometriosis, and a higher prevalence is found among women with infertility. Although endometriosis is commonly observed in women who are infertile, ...

Endometriosis - tissue usually found inside the uterus that grows outside - thrives because of altered cellular signaling that is mediated by estrogen, said researchers from Baylor College of Medicine in a report that appears ...

A novel study shows women who undergo surgical treatment for endometriosis have a lower risk of developing ovarian cancer. According to results published in Acta Obstetricia et Gynecologica Scandinavica, a journal of the ...

Scientists report that they now know how to build a molecular Trojan horse that can penetrate gram-negative bacteria, solving a problem that for decades has stalled the development of effective new antibiotics against these ...

Using gene sequencing tools, scientists from Johns Hopkins Medicine and the University of British Columbia have found a set of genetic mutations in samples from 24 women with benign endometriosis, a painful disorder marked ...

A natural mechanism by which our cells kill the bacterium responsible for tuberculosis (TB) has been discovered by scientists at the Francis Crick Institute, which could help in the battle against antibiotic-resistant bacteria.

The largest observational study to date of dairy intakes and bone and frailty measurements in older adults has found that increased yogurt consumption was associated with a higher hip bone density and a significantly reduced ...

Mothers infected with malaria during pregnancy can pass more of their own cells to their baby and change the infant's risk of later infection, a new study shows.

Acid reflux and heartburn affect more than 20 percent of the U.S. population, but common medications to treat the disease might not work for a large portion people who suffer from the diseases.

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Stanford lab grows cornea cells for transplant – The Mercury News

PALO ALTO A Stanford research team has created a potentially powerful new way to fix damaged corneas a major source of vision problems and blindness.

Millions of new eye cells are being grown in a Palo Alto lab, enlisting one of medicines most important and promising new tools: refurbishing diseased and damaged tissue with healthy new cells.

One of the exciting possibilities of this cellular approach is that one donor cornea, which contributes a few parent cells, can generate enough cells to treat tens or hundreds of patients, said lead researcher Dr. Jeffrey Goldberg, professor and chairman of the Department of Ophthalmology at the Stanford University School of Medicine.

About 100,000 corneal transplants are done annually in the United States but they require surgery with donated corneas from cadavers. The procedure fails nearly a third of the time, and there arent enough high-quality donor corneas to go around.

Other scientists have been trying to grow full corneas from scratch, attaching a fragile film of cells to a membrane. Thats a challenging bioengineering problem.

Stanfords innovative strategy, eight years in the making, is to grow individual cells instead. The team then harvests a few mother corneal cells, called progenitor cells, donated from a cadaver.

These cells are then put into a warm broth in petri dishes, where they give birth to many new young corneal cells.

The cells are being grown at Stanfords new Laboratory for Cell and Gene Medicine, a 25,000-square-foot biological manufacturing facility on Palo Altos California Avenue.

The Stanford team enlisted a recent technological advance: magnetic nanoparticles. The particles are incredibly small, measuring only 50 nanometers in diameter. By comparison, a human hair is 75,000 nanometers in diameter.

The new young cells were magnetized with the nanoparticles, loaded into a syringe and injected into the eye.Then, using an electromagnetic force on a patch held outside of the eye, the team pulled the cells into the middle of the eye, to the back of cornea. Later, the magnetic nanoparticles fell off the cells, exited the eye and were excreted in the patients urine.

Ultimately, Goldberg said, the team hopes to mass produce off-the-shelf cells that can be easily transplanted into patients with severe damage to the cornea, the transparent outer coating of the eye that covers the iris and pupil.

In the first trial of 11 patients, a so-called Phase 1 trial, the team only studied safety.

Not only was the procedure safe, but we are seeing hints of efficacy that we are very excited about, Goldberg said. Were cautiously optimistic.

The Stanford team plans to expand the study in September to Phase 2 to measure how the vision of the patients improves.

The effort has been endorsed by the American Academy of Ophthalmology, which says it supports innovative clinical Many countries outside the United States and Europe have a shortage of donor eye tissue, leaving millions of people unable to obtain a donor cornea. If this early research is found to be safe and effective, this technique may help some patients avoid corneal transplant, said Dr. Philip R. Rizzuto, clinical spokesman for the American Academy of Ophthalmology.

If successful, the approach could also be used to replace other types of damaged eye cells, offering therapies for retinal and optic nerve diseases including glaucoma, the leading cause of irreversible blindness, he said.

The approach is part of an expanding field of lab-grown cell therapies. Sheets of healthy skin are used to treat burns, chronic skin wounds and diseases like epidermolysis bullosa, which causes incurable blistering. And bioengineered cartilage is increasingly used to treat certain knee injuries.

Stanford researchers believe that lab-grown corneal cells could become another important type of regenerative medicine.

Unlike other transplants, corneas in the Stanford teams approach dont have to be a perfect match. Rejection can be prevented with simple topical eyedrops.

Goldberg predicted that the approach could eventually replace about 80 percent of corneal transplants.

Specifically, it could repair the damaged inner layer of the cornea, called the endothelium, as seen in diseases like Fuchs dystrophy, which causes corneal damage due to swelling. It would not help in the 20 percent of transplants needed to fix the middle layer of the cornea, called the stroma.

Next month, the team will analyze its early Phase 1 data and also apply for permission from the U.S. Food and Drug Administration to begin Phase 2.

While relatively few people in the United States suffer diseases or injuries that cause devastating cornea damage, the numbers are much greater in developing nations, where infectious eye diseases remain common.

The new approach could offer a nonsurgical permanent solution in those countries, Goldberg said.

Half the world has no access to tissue, he said. I would love this to be one and done, solving patients problems for decades.

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Stanford lab grows cornea cells for transplant - The Mercury News

The Daily Pennsylvanian | How Penn Medicine and people from … – The Daily Pennsylvanian

Penn Medicines new Center for Digital Health will serve as a connection between technology, social media and healthcare.

Astudy led in part by Penn scientistsexamined the DNA of over10,500 Pakistanis in order to guide research on treatments for heart disease.

Many drugs developed to lower heart disease havetargeted a gene linked to arterial plaque, Science Magazine explained. But this study found that the absence of this gene may not greatly affect one's risk for heart disease.

Instead, the study found that the absence of a different gene called APOC3 might help.

Penn professor Danish Saleheen and other researchers searched Pakistan for individuals missing a functional copy ofthe gene. Many Pakistanis marry their first cousins, so parents more frequently pass on identical copies of a gene to their children meaning that they're also more likely to pass on two nonfunctional copies.

People with these deficient copies of agene are known as genetic knockouts, Philly.com explained. Scientists can deliberately breed animals to produce knockouts, but they must survey large numbers of peopleto find them in humans.

The researchers found a man,woman and their nine children in Pakistan who were all APOC3 knockouts.

When they consumed a high-fat meal, study participants without functioningAPOC3 genes did not experience elevated levels of plasma triglycerides, according toPenn Medicine. Higher levels of triglycerides are abiomarker of heart disease risk.

The family seemed healthy otherwise, which could suggest that missing the function of the APOC3 gene could help treat heart disease without other, harmful effects, Science Magazine noted.

Saleheen told Penn Medicine that these were the worlds first APOC3 knockouts found. Hes been working in Pakistan for over 10 years, amassing as many blood samples as possible, to identify different genetic knockouts so far hes found over 1,300 in over 70,000 participants, a figure he hopes will eventually surpass 200,000 as the work continues.

The study was led by Penn's Perelman School of Medicine, the Center For Non-Communicable Diseases in Pakistan, the Broad Institute of MIT and Harvard and the University of Cambridge.

Co-senior author of the studySekar Kathiresan told Science Magazine that he hopes this work will lead to a "Human Knockout Project," similar in caliber to the Human Genome Project, in order to aggregate data on knockouts.

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The Daily Pennsylvanian | How Penn Medicine and people from ... - The Daily Pennsylvanian

Gene Findings Advance Precision Medicine for Intellectual Disability – Genetic Engineering & Biotechnology News

Scientists at the Centre for Addiction and Mental Health (CAMH) and Queen's University have identified 26 new genes linked to intellectual disability. Currently most patients with intellectual disability receive no molecular diagnosis, significantly affecting their health and shortening their lifespan, according to the researchers.

The study ("Mapping Autosomal Recessive Intellectual Disability: Combined Microarray and Exome Sequencing Identifies 26 Novel Candidate Genes in 192 Consanguineous Families"),published inMolecular Psychiatry, has implications for the diagnosis and clinical care of those affected, and also adds to the growing knowledge of brain development and functioning. It may eventually lead to personalized treatments for affected individuals. Interestingly, some of the genes identified are thought to be connected with autism spectrum disorders, notes John Vincent, Ph.D.,team leader and senior scientist who heads the MiND (Molecular Neuropsychiatry and Development) Laboratory in theCampbell Family Mental Health Research Instituteat CAMH.

"This is the largest study of its kind on intellectual disability to come out of North America," he adds.

More than one in 100 children worldwide are affected by intellectual disability, which is characterized by significant limitations in learning that also affect their day-to-day lives. Frequently, intellectual disability also accompanies symptoms of autism spectrum disorders, and many genes have been found to be shared by the two illnesses.

The study involved 192 families from Pakistan and Iran with more than one affected family member. Intellectual disability is frequently caused by recessive genes, meaning that an affected child gets a defective copy of the gene from each parent.

The families in the study all had a history of marriage among relatives, which occurs quite commonly in communities in South Asia, the Middle East, and Africa. Studying families with this background, and multiple affected individuals, can enable researchers to identify disease genes that would otherwise remain hidden.

The Canadian research team pinpointed mutations related to intellectual disability in half of these 192 families, in 72 different genes. The identification of 26 new genes adds to 11 new genes that the team had previously linked to intellectual disability.

One immediate implication of the study is to prevent future cases of intellectual disability, the researchers say. Unaffected family members and relatives could be genetically screened to see if they carry these mutations and provided with counselling on the risks of "within-family" marriages.

A broader goal is to develop diagnostic screening tools that are also relevant to populations in which "within-family" marriages are rare, such as Canada, U.S., Japan, China, and Europe. Ultimately, this information would be used to plan more personalized treatment.

While 26 genes may seem a substantial number, there are likely hundreds of genes that, when defective, may lead to intellectual disability. "The strategy we have used speeds up the process of identifying disease genes and of enabling diagnostic labs to deliver more accurate information for clinicians and families," explains Dr. Vincent.

This strategy involves various genetic techniques, including microarray genotyping and whole-exome sequencing, and studying families with a history of marriage among relatives.

"There's an opportunity now to further explore the functioning and biological pathways of these genes, and to help complete the picture of how the central nervous system works," continued Dr. Vincent. "Knowing the genes involved is a big step forward, but understanding how they function is also crucial before we can start planning treatments or even cures."

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Gene Findings Advance Precision Medicine for Intellectual Disability - Genetic Engineering & Biotechnology News

Here’s Another Way CRISPR Is Changing Medicine – TIME

Gene editing, through a technology called CRISPR , can edit DNA almost as easily as a word processor edits text. Now that system is being used to diagnose the presence of cancer and to create on-the-spot tests for infections like Zika virus , according to a new report published in the journal Science from researchers at the Broad Institute of MIT and Harvard.

CRISPR-cas9, first described in 2012, gives scientists the genetic equivalent of a word processing cursor, allowing them to home in on specific parts of a genome to delete, insert, copy, cut or paste DNA at will. In the current paper, Feng Zhang , associate professor of biological engineering and brain and cognitive sciences at MIT and a member of the Broad Institute, and his colleagues modified the CRISPR system so that it recognized the products churned out by genes as well. They used CRISPR to recognize specific substances that bacteria and viruses make. Picking up even the slightest whisper of these products can alert doctors that an infection is active.

The system, dubbed SHERLOCK, could accurately distinguish between Zika virus and dengue virus from blood, urine and saliva samples. SHERLOCK could also provide the answer more quickly than current tests. Now, it takes several days for doctors to culture microbes like bacteria or viruses in order to confirm that they are present. SHERLOCK, says Zhang, could identify a bacteria or virus in 30 minutes to an hour.

MORE : CRISPR Technology Scientists on Their Gene Editing Tool

In Zhangs tests, SHERLOCK also provided a way to measure how much virus was there, giving doctors a better sense of how entrenched the infection might be.

SHERLOCK could also pick up mutations present in tumors from patients blood. Such blood-based tests for cancer, or liquid biopsies , are a promising area of cancer research, and having a CRISPR-based tool like SHERLOCK could speed their development.

Zhang anticipates that the technology could also be critical in the fight against antibiotic resistance; SHERLOCK could determine if a persons bacterial infection is already resistant to certain antibiotics, for example, which would help doctors to avoid those drugs. It could also pick up when a persons infection starts to become resistant to the drug so doctors can switch a patients antibiotic to better fight the bacterial infection.

MORE : 5 Common Myths About Antibiotic-Resistant Bacteria

This new CRISPR based platform has the potential to be developed as a point of care diagnostic that could be as easy to use as an at-home pregnancy test, says James Collins, member of the Broad and professor of engineering at MIT.

The CRISPR system just requires a kit designed to recognize the bacteria, virus or cancer mutation in question, and those are relatively cheap and accessible. Zhangs team predicts some tests could cost less than $1. That could make it a mainstay in lower-resource countries when infectious like Zika or even Ebola emerge, by helping people to get treatment sooner so that the breadth of the outbreak is contained.

We want to deploy this in an area where it can make a real difference, says Zhang.

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Here's Another Way CRISPR Is Changing Medicine - TIME

Consensus Study on Human Gene Editing – National-Academies.org

Consensus Study

Background

With the conclusion of the International Summit on Human Gene Editing, the second component of the Human Gene-Editing Initiative began: a comprehensive study of the scientific underpinnings of human gene-editing technologies, their potential use in biomedical research and medicine -- including human germline editing -- and the clinical, ethical, legal, and social implications of their use.

A multidisciplinary committee of expertsbegan its information-gathering process at the summit, and over the past year performed its own independent and in-depth review of the science and policy of human gene editing by reviewing the literature and holding data-gathering meetings in the U.S. and abroad to solicit broad input from researchers, clinicians, policymakers, and the public. The committee also monitored for the latest scientific achievements of importance in this rapidly developing field.

While informed by the statement issued by the organizing committee for the international summit, the consensus study committee had broad discretion to arrive at its own findings and conclusions. The committee's report represents the official views of NAS and NAM.

Moreabout the study| Info onpublic meetings | Answers tofrequently asked questions

Human Genome Editing: Science, Ethics, and Governance

Genome editing is a powerful new tool for making precise alterations to an organisms genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions.

In Human Genome Editing: Science, Ethics, and Governance, a new report from the National Academy of Sciences and National Academy of Medicine, an expert committee considers important questions about the human application of genome editing including: Balancing potential benefits with unintended risks, governing the use of genome editing, incorporating societal values into clinical applications and policy decisions, and respecting the inevitable differences across nations and cultures that will shape how and whether to use these new technologies. The committee sets forth criteria that must be met before permitting clinical trials of heritable germline editing, provides conclusions on the crucial need for public education and engagement, and presents seven general principles for the governance of human genome editing.

A Report Highlights brief is available:

The following one-pagers are also available:

Watch the archived video webcast of the report release briefing, held Feb. 14, 2017.

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Consensus Study on Human Gene Editing - National-Academies.org

FDA Continues Strong Support of Innovation in Development of Gene Therapy Products – FDA.gov

For Immediate Release: January 28, 2020

This is a pivotal time in the field of gene therapy as the FDA continues its efforts to support innovators developing new medical products for Americans and others around the world. To date, the FDA has approved four gene therapy products, which insert new genetic material into a patients cells. The agency anticipates many more approvals in the coming years, as evidenced by the more than 900 investigational new drug (IND) applications for ongoing clinical studies in this area. The FDA believes this will provide patients and providers with increased therapeutic choices.

In that spirit, today, the FDA is announcing the release of a number of important policies: six final guidances on gene therapy manufacturing and clinical development of products and a draft guidance, Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations.

The growth of innovative research and product development in the field of gene therapy is exciting to us as physicians, scientists and regulators, said FDA Commissioner Stephen M. Hahn, M.D. We understand and appreciate the tremendous impact that gene therapies can have on patients by potentially reversing the debilitating trajectory of diseases. These therapies, once only conceptual, are rapidly becoming a therapeutic reality for an increasing number of patients with a wide range of diseases, including rare genetic disorders and autoimmune diseases.

As the regulators of these novel therapies, we know that the framework we construct for product development and review will set the stage for continued advancement of this cutting-edge field and further enable innovators to safely develop effective therapies for many diseases with unmet medical needs, said Peter Marks, M.D., Ph.D., director of the FDAs Center for Biologics Evaluation and Research. Scientific development in this area is fast-paced, complex, and poses many unique questions during a product review; including how these products work, how to administer them safely, and whether they will continue to achieve a therapeutic effect in the body without causing adverse side effects over a long period of time.

One of the most important steps the FDA can take to support safe innovation in this field is to create policies that provide product developers with meaningful guidance to answer critical questions as they research and design their gene therapy products.

The six final guidances issued today provide the agencys recommendations for product developers on manufacturing issues and recommendations for those focusing on gene therapy products to address specific disease areas. The six guidance documents incorporate input from many stakeholders and take a significant step toward helping to shape the modern structure for the development and manufacture of gene therapies. The agency is issuing this suite of documents to help advance the field of gene therapy while providing recommendations to help ensure that these innovative products meet the FDAs standards for safety and effectiveness.

The scientific review of gene therapies includes the need to evaluate highly complex information on product manufacturing and quality. In addition, the clinical review of these products frequently poses more challenging questions to regulators than reviews of more conventional drugs, such as questions about the durability of response, and these questions often cant be fully answered in pre-market trials of reasonable size and duration. For some gene therapy products, therefore, although they have met the FDAs standards for approval, we may need to accept some level of uncertainty around questions of the duration of the response at the time of marketing authorization. Effective tools for reliable post-market follow up, such as post-market clinical trials, are going to be key to advancing this field and helping to ensure that our approach fosters safe and innovative treatments.

The draft guidance on interpreting sameness of gene therapy products under the orphan drug regulations provides the FDAs proposed current thinking on an interpretation of sameness between gene therapy products for the purposes of obtaining orphan-drug designation and eligibility for orphan-drug exclusivity. The draft guidance focuses on how the FDA will evaluate differences between gene therapy products when they are intended to treat the same disease. As laid out in the draft guidance and our regulations, the agencys determination will consider the principal molecular structural features of the gene therapy products, which includes transgenes (the transferred gene) and vectors (the vehicle for delivering the transgene to a cell).

With the large volume of products currently being studied, gene therapy product developers have asked the agency important questions about orphan-drug designation incentives to develop products for rare diseases with very small patient populations. The draft guidance has potential positive implications both for product developers and patients by providing insight into the agencys most current thinking on the sameness of products, and thus, not discourage the development of multiple gene therapy products to treat the same disease or condition. For patients, this policy could help lead to the development and approval of multiple treatments, creating a more competitive market with choices. We encourage stakeholders to provide their comments.

In sum, these policy documents are representative of efforts to help advance product development in the field of gene therapy. We will continue to work with product innovators, sponsors, researchers, patients, and other stakeholders to help make the development and review of these products more efficient, while putting in place the regulatory controls needed to ensure that the resulting therapies are both safe and effective. We also encourage developers of new gene therapy products to make full use of our expedited programs available for products intended to address unmet medical needs in the treatment of serious or life-threatening conditions. These programs include breakthrough therapy designation, regenerative medicine advanced therapy designation, and fast track designation, as well as priority review and accelerated approval. Developers should pursue these programs whenever possible to help bring the benefits of important advances to patients as soon as possible. We believe our work will help advance innovations in a way that assures their safety and effectiveness, provides new therapeutic choices to patients and providers and continues to build confidence in this novel and emerging area of medicine.

The FDA is an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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FDA Continues Strong Support of Innovation in Development of Gene Therapy Products - FDA.gov

Rethinking anorexia: Biology may be more important than culture, new studies reveal – Science Magazine

By Jennifer Couzin-FrankelApr. 9, 2020 , 11:35 AM

In college in the 1990s, Alix Timko wondered why she and her friends didnt have eating disorders. We were all in our late teens, early 20s, all vaguely dissatisfied with how we looked, says Timko, now a psychologist at Childrens Hospital of Philadelphia. Her crowd of friends matched the profile she had seen in TV dramasoverachievers who exercised regularly and whose eating was erratic, hours of fasting followed by a huge pizza.

My friends and I should have had eating disorders, she says. And we didnt.

It was an early clue that her understanding of eating disorders was off the mark, especially for the direst diagnosis of all: anorexia nervosa. Anorexia is estimated to affect just under 1% of the U.S. population, with many more who may go undiagnosed. The illness manifests as self-starvation and weight loss so extreme that it can send the body into a state resembling hibernation. Although the disorder also affects boys and men, those who have it are most often female, and about 10% of those affected die. Thats the highest mortality rate of any psychiatric condition after substance abuse, on par with that of childhood leukemia. With current treatments, about half of adolescents recover, and another 20% to 30% are helped.

As a young adult, Timko shared the prevailing view of the disease: that it develops when girls, motivated by a culture that worships thinness, exert extreme willpower to stop themselves from eating. Often, the idea went, the behavior arises in reaction to parents who are unloving, controlling, or worse. But when Timko began to treat teens with anorexia and their families, that narrative crumbledand so did her certainties about who is at risk. Many of those young people dont have body dissatisfaction, they werent on a diet, its not about control, she found. Their mom and dad are fabulous and would move heaven and Earth to get them better.

Timko wasnt alone. Other researchers were also questioning psychological theories of anorexia that had reigned for generations. Hunger is a basic drive, says Cynthia Bulik, a clinical psychologist who runs eating disorder centers at the University of North Carolina, Chapel Hill, and at the Karolinska Institute. The idea that patients use willpower to override hunger never rang true, she says. My patients have said for years that when they starve, they feel better. She began to consider another possibility: What if their biology is driving them to eschew food?

Bulik and Timko are now part of a small band of researchers working to untangle the biology of anorexia. The more they look, the more they find to suggest the diseases biological roots run deep. For instance, genetic studies indicate its about as heritable as obesity or depression. The circuitry of the brains reward system behaves differently in unaffected volunteers than in people with anorexia and those who have recovered. And new treatments drawing on biology are being tested, including deep-brain stimulation and psychedelic drugs. Those experiments aim not only to improve the outlook for patients, but also to explore how closely the disease aligns with others across psychiatry, including obsessive-compulsive disorder (OCD) and addiction.

Scientists pursuing those new ideas face a challenge, in part because of money: For fiscal year 2019, anorexia got $11 million in funding from the National Institutes of Health (NIH), a figure that hasnt changed notably in many years and that researchers decry as shockingly low given the diseases burdens. By contrast, schizophreniawhich has a similar prevalence and also surges during adolescencegarnered $263 million. The dearth of funder interest, many say, springs from the view that anorexias roots are cultural, along with shame and stigma still clouding the disease. But evidence is mounting that biology is at its core.

Many researchers lament that eating disorders, including anorexia nervosa, are underfunded given their prevalence. These numbers are drawn from 2017 data for the United States; the number of individuals affected is an estimate.

(GRAPHIC) X. LIU/SCIENCE; (DATA) BRYN AUSTIN/BOSTON CHILDRENS HOSPITAL; NATIONAL INSTITUTES OF HEALTH

Lori Zeltser pivotedto anorexia from studying obesity. A developmental neuroscientist at Columbia University, she studied the brains of developing mice, trying to identify feeding circuits that increase susceptibility to obesity in adulthood. Then about 10 years ago, Zeltser saw a notice for funding from the Klarman Family Foundation, formed by hedge fund manager Seth Klarman and his wife, Beth, now the foundations president. The foundation wanted to stimulate basic research into eating disorders, and because of Zeltsers research on appetite, she submitted a proposal.

To get up to speed on anorexia, Zeltser turned to the literature. Researchers in Sweden and Minnesota had compared anorexia rates in identical and fraternal twins, a common approach to tease out heritability of complex traits and diseases. Those reports showed that 50% to 60% of the risk of developing anorexia was due to genes, implying DNA is a powerful driver. By contrast, family studies suggest the heritability of breast cancer is about 30%, and that of depression is roughly 40%. I was shocked, Zeltser says.

Layered on the genetics work was a data point that caught Zeltsers attention. An antipsychotic drug, olanzapine, which causes profound weight gain as a side effect, had little to no effect on weight when tested in people with anorexia. Something in peoples biology prevented olanzapine from causing weight gain, Zeltser believes. That is not just [mental] control.

But a deep schism remains, with many practitioners concerned that biology is getting more attention than it deserves. If I had to choose nature versus nurture in the development of anorexia and other eating disorders, I would choose nurture, says Margo Maine, a psychologist who has treated eating disorders for years. Eating disorders are primarily female, she says, in part because gender is a cultural experience.

Psychotherapist Carolyn Costin, who recovered from anorexia in the late 1970s and established a network of private treatment centers around the United States, says biology plays a role but that cultural messages and psychological stressors are also important factors. She worries especially that the way biology research is described could discourage patients about their prospects for recovery. About 8 years ago, she says, Clients started coming in, saying, Its genetic, why bother trying to get well?

Such comments agitate researchers like Bulik. The patients she treats, she says, are reassured, not distressed, to learn that the disorder is rooted in biology and that biology doesnt translate into destiny. Although she, Zeltser, and others agree that anorexia has environmental drivers, as most chronic conditions do, they object to the idea that environment leads the way. Exposure to this ideal [of thinness] is ubiquitous, but everybody doesnt get anorexia nervosa, Bulik says. None of the sociocultural literature has ever been able to explain why. She adds, A lot of patients will say, It was never about being thin for me, ever.

If you look at psychiatric syndromes over 200 years, anorexia hasnt changed at all, whereas our culture has, says James Lock, a child psychiatrist who heads the child and adolescent eating disorders program at Stanford University School of Medicine.

To begin digging into the biology of anorexia, Zeltser used a 2010 grant from the Klarman foundation to build a mouse model of the disease. Because feeding is easy to measure, she reasoned that anorexias restrained feeding behavior is well-suited for animal modeling. Her goal was to study the eating and starvation patterns of the mice and explore how genetics and the environment interact to trigger the disorder.

In a 2016 issue ofTranslational Psychiatry,Zeltser described micewith a variant in a gene that in people is linked to anorexia. On its own, the variant didnt noticeably affect mouse feeding behavior. To mimic the pullback from eating that often precedes a diagnosis, the researchers restricted the animals caloric intake by 20% to 30%. Then they induced stress, another factor linked to anorexia, by housing the normally social animals alone. The result: The mice stop eating, Zeltser says.

Lori Zeltser, a developmental neuroscientist at Columbia University, has developed a mouse model of anorexia nervosa.

Zeltser is talking with clinical colleagues about comparing her rodents behavior with videos of patients in a feeding lab, where researchers observe how much people eat, which nutrients they choose, and which they avoid. If the behaviors seem parallel, the mice could help point the way to new treatments or even different environments that could better support eating.

But publishing her animal work has proved difficult. Zeltser is often asked, How do you know if what youre finding is relevant to humans? Thats a common question of anyone doing mouse work, but Zeltser says the challenge here runs deeper. This is not taken seriously as a disease that has a biological basis, she says. Instead, its dismissed as extreme girl behavior and oh my God, theyre crazy, pushback she finds immensely frustrating.

Accumulating genetic data could change that by making anorexias biological roots harder to ignore. Some of the strongest evidence emerged last summer, when Bulik and others published inNature Geneticsthe largest genetics study on the disease, with roughly $9 million in funding from the Klarman foundation and additional funds from NIH. By analyzing the genomes of nearly 17,000 people with anorexia and more than 55,000 people without, the researchers identified eight statistically significant genomic regions, along with other patterns of genetic associations that yielded important clues. Some of those associations tracked with results of studies of other psychiatric illnesses, including OCD and depression, which didnt surprise Bulik. What did were overlapping associations with DNA controlling body mass index (BMI), lipids, and other metabolic traits.

We said, This doesnt look like any other psychiatric disorder, Bulik says. It might be the inverse of obesitythese people might be genetically predisposed to low BMI. In the February 2019 issue of theJournal of the American Academy of Child & Adolescent Psychiatry, she and her teamsifted through BMI recordsfor young people later diagnosed with anorexia and other eating disorders. The BMIs of 243 people diagnosed with anorexia began to diverge from those of a control group before they started kindergarten.

Bulik is now launchingthe Eating Disorders Genetics Initiative, with more than $7 million from NIH, additional funding from Sweden and the United Kingdom, and potential infusions from other countries and individual donors. The initiative aims to include 100,000 people with anorexia nervosa, bulimia nervosa, and binge eating disorder. Although genetics is unlikely to offer quick solutions, Bulik hopes it can shine the light in the direction you need to go for effective therapies, including medications.

The genetic findingsmight one day intersect with another line of research: studies of brain structures and signaling that are revealing tantalizing differences between people with and without anorexia. At Columbia, psychiatrist Joanna Steinglass wanted to understand how the brains of people with anorexia guide their food choices. In two studies, she and her colleagues recruited inpatients with eating disorders along with a control group. In people with anorexia, both during and after hospitalization, MRI scans showed the region of the brain associated with selecting foods was the dorsal striatum, which is key to forming habits. In people without an eating disorder, a different brain region guides choices. The work first appearedin 2015 inNature Neuroscience, and the team presented more findings at a conference last year.

Theyre using different circuits when they make decisions, Steinglass says. This jibes with her idea that as people repeatedly restrict eating, the behavior moves to a different brain region and becomes less amenable to change. That could help explain why many recovered patients relapse.

Another clue to how the brain might throw eating off trackwas reported last month inThe American Journal of Psychiatry. Walter Kaye, a psychiatrist who directs the eating disorders program at the University of California (UC), San Diego, led a study looking at how the brains of people with anorexia behave when their bodies are hungry. Kaye, whose program treats about 70 patients per day, ran a study that included 48 women, 26 of whom had anorexia. Each was studied twice with brain imaging, once immediately after a meal and, on a separate visit, after fasting for 16 hours.

Kaye knew hunger activates brain circuits that in turn motivate eating, making food desirable. That relationship was clear during brain imaging of the control group volunteers: When they were offered sugar water after 16 hours of fasting, their reward and motivation circuits lit up. But in people with anorexia, those circuits were much less active after fasting. They could identify being hungry, Kaye says, but their brains couldnt convert that into a desire to eat. The patients also experienced heightened anxiety and inhibition, along with diminished reward signaling in their brains. That effect may further impair their drive to eat. Kaye suggests people with anorexia miscode food as risky rather than rewarding.

A lot of patients will say, It was never about being thin for me, ever.

Psychiatrist Rebecca Park at the University of Oxford also suspects the disease hijacks the brains reward system. Some of her patients experience this sense of aberrant reward, almost a high from starvation, she says. Parks neuroscience research indicates aberrant brain responses to reward cues.

Are those brain differences a cause or a result of starvation? Studying people in remission eliminates the effects of malnutrition on the brain but cant definitively answer the question. Its likely that starvation in adolescence is going to damage your brain, Park says. One way to begin to disentangle whether the brain differences predate the disease is to study people very early in its course. Steinglass is in the third year of a brain scanning study of reward circuitry, which now includes 55 recently diagnosed teenagers and a control group of 25 others. The coronavirus pandemic has halted enrollment for now, but Steinglass hopes to have results in 2 to 3 years. Other researchers are working to understand how, and to what degree, the brain recovers once eating resumes.

Theres an overall sensethat were joining the rest of the world by finally applying scientific methods to anorexia nervosa, Steinglass says. The ultimate goal is new treatments, which are sorely needed.

The most studied and most effective strategy to date is called family-based treatment (FBT), which originated at the Maudsley Hospital in London. It was later refined by Lock and psychologist Daniel Le Grange, of UC San Francisco, who trained at Maudsley.

FBT asks parents to set aside many of their familys day-to-day activitiesscaling back school, work, hobbiesto sit with their children, requiring them to eat. Faced with food as a form of medicine, and with their world having contracted, many young people do start to eat again despite the fear and anxiety it causes them. Researchers are working to understand how FBT is intertwined with the biology of the illness, but for about half who try FBT in adolescenceand perhaps 70% who try it early in the diseasethe treatment is effective.

But many families arent told about that therapeutic strategy, even though decades have passed since it first showed success in a randomized trial, in 1987. Practitioners may not be familiar with FBT, Timko says, they may believe the family played a role in anorexias onset, or they may feel that adolescents must want to get better before starting FBTa view she disputes.

Laura Collins Lyster-Mensh experienced the regimen up close after her daughter Olympia, then 14, stopped eating one day in 2002. Lyster-Mensh says a succession of therapists urged her and her husband to stand back and let Olympia eat when she was ready. Meanwhile, her weight continued to spiral downward. We had been told she wouldnt recover, families were really at fault, to back off and let her do this on her own, Lyster-Mensh says. Then she learned about FBT from a newspaper article and raced to try it.

The first agonizing meals took hours, while Olympia mashed her food into a pulp or cried and raged at her parents. I know families whose kids have jumped out of moving cars to avoid a sandwich, says Lyster-Mensh, echoing comments of many clinicians who describe patients crushing fear of food. Olympia ultimately recovered, although not without challenges that included a relapse during college.

The young patients treated with FBT who do start to eat again do well on the one measure that predicts longer-term prognosis: early weight gain. In 2019, a study in theEuropean Eating Disorders Reviewled by Le Grange confirmed earlier research showing thatgaining about 2.3 kilograms in the first month of treatment is a predictor of health1 year later. Girls with anorexia who boosted their calorie intake and gained weight experienced increases in estrogen levels (which plummet in starvation), reduced stress, and improved ability to navigate different situations, a psychological trait called flexibility.

Researchers are exploring ways to build on and improve FBTor find new strategies to help patients in whom it has failed. Some clinical trials are testing whether certain talk therapies, such as cognitive behavioural therapy to help patients reframe their thinking, can helpfor example, by reducing anxiety or other impediments to eating.

New biological models of anorexia hint at other kinds of interventions. An 18-person study at Johns Hopkins University is offering the psychedelic drug psilocybin to patients. Early data suggest it holds promise in helping smokers quit and combating alcoholismand many researchers believe that in certain ways, anorexia shares some features with addiction. Park is leading a seven-person study of deep-brain stimulation in people with severe enduring anorexia, some of whom also have OCD.

Theres a certain neural network thats well characterized in OCD, she says, and disrupting the signaling in that network with deep-brain stimulation can help those patients. Because OCD and anorexia have shared features and some genetic links, shes interested in whether disrupting the same neural network might also help people with the eating disorder.

Still, studies remain sparse, Lock says. With limited funding, theres little chance of attracting new scientists to a small field. As researchers, you dont want to go to the pot thats empty, he says. Why arent we investing more? Its especially frustrating because, Lock points out, many patients with anorexia successfully heal and enjoy a bright future. What [other] illness in psychiatry can you say you cure? he asks.

For families, regardless of whether a patient recovers, the shame can persistand with it hesitation to speak up and lobby for funding. Lyster-Mensh is an exception. After her familys experience, she began to voice support for evidence-based treatmentfirst in a memoir,Eating with Your Anorexic, which she wrote under the name Laura Collins, and then throughFEAST, a message board turned advocacy group.

Its still a pretty small group, Lyster-Mensh says, of those willing to speak openly. Most families are so burned out, crushed, guilty, that they dont want to come forward, she says. There are still these myths out therethat these are chosen illnesses and parents somehow failed to prevent, or caused, or exacerbated the problem. Still, she hopes that as researchers doggedly track the diseases biological roots in genes and the brain, those enduring myths will fade.

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Rethinking anorexia: Biology may be more important than culture, new studies reveal - Science Magazine

WSU sleep researchers discover why some people may toss and turn more than others – The Spokesman-Review

UPDATED: Fri., April 14, 2017, 10:04 p.m.

Elson S. Floyd College of Medicine assistant research professor Jason Gerstner leads the research team studying fruit flies brains and sleep patterns. (Dan Pelle / The Spokesman-Review)

A research team led by a Washington State University biochemist could help scientists shed light on why we need to sleep, and why some people have an easier time resting than others.

Jason Gerstner, a research assistant professor at WSUs Elson S. Floyd College of Medicine, found that mutations in a sleep gene in the brain can cause humans, mice and fruit flies to have less restful sleep.

The results of the study were published in a peer-reviewed article in the journal Science Advances earlier this month.

It might sound odd, but scientists still arent sure why sleep is necessary. One theory is that sleep helps with memory formation and the brains growth and change: what scientists call neuroplasticity. Other theories maintain that sleep is restorative for the body and that it lowers metabolism, helping to conserve energy.

We still dont fully understand what biological function sleep is serving, Gerstner said. One of the ways we can get at answering that question is through examining neurobiological pathways.

Much of Gerstners research has focused on a particular gene, FABP7, thats been linked to sleep function. In previous research, Gerstner saw the genes expression cycles naturally during the day in mice, mirroring sleep-wake cycles.

For this study, Gerstners team looked at a sleep study of Japanese men, some of whom had a naturally occurring mutation in their FABP7 gene. Men with the mutation slept about as long as men without it, but their sleep was more fitful, with more bouts of time spent awake during the night.

Men with the mutation also reported more symptoms indicating clinical depression on an assessment, though neither group scored high enough to meet the criteria for depression. Gerstner said that suggests either the gene mutation itself or sleep disturbance might be linked to depression in some way.

There were no significant differences in health, age or sleepiness between the two groups of men.

The study showed similar restlessness in rats that had their FABP7 genes knocked out and in genetically engineered fruit flies with the same gene mutation. Because the mutation works the same way across species, its a promising finding for future research, and even for treatment of sleep disorders.

The FABP7 mutation causes the gene to create a different protein sequence. That affects which other proteins in the brain the sequences bind to, which in turn can influence a broad range of functions, like gene expression, inflammation and other brain functions.

The researchers also found the specific part of the brain, a star-shaped cell called an astrocyte, where FABP7 plays a role in sleep.

Previously, those cells were thought to be support cells for neurons, Gerstner said. Now, scientists are learning theyre important in their own right.

This is some of the earliest evidence that astrocytes really play a role in sleep, said Isaac Perron, a doctoral student in neurobiology at the University of Pennsylvania who worked with mice in the experiment.

Perrons interest is in sleep and nutrition. Because the proteins coded by FABP7 bind with fatty acids like omega-3s, he thinks the gene might be a link in showing how the fatty acids we eat can influence brain functions, including sleep.

Jerry Yin, a professor of genetics at the University of Wisconsin-Madison, who worked on the fruit fly portion of the research, said finding a common pathway like FABP7 helps people looking at medications or gene therapies target their treatments.

Knowing FABP7 works in astrocytes helps researchers tailor their focus, since those cells are where youre likely to have an effect manipulating this gene, Yin said.

Testing a therapy or medication is also easier because the FABP7 impact on sleep works in fruit flies and mice, both of which are commonly used in research.

Since weve narrowed down particular protein expressed within astrocytes, it underscores the importance of these cells in regulating complex behavior across species, Gerstner said.

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WSU sleep researchers discover why some people may toss and turn more than others - The Spokesman-Review

Gene and Associated Protein May be Key to Slow Alzheimer’s Progression – Clinical OMICs News

A team of investigators from Case Western Reserve School of Medicine, say they have identified a gene and associated protein that previously had not been associated with Alzheimers disease (AD), which could potentially be suppressed to slow the progression of Alzheimers disease.

The research was published this month by the journal Nature Communications, and supported by grants from the National Institutes of Health (NIH) and the Alzheimers Association.

For the research led by Xinglong Wang, an associate professor of pathology at the School of Medicine, the team correlated roughly 1 million single nucleotide polymorphisms (SNPs) with brain images obtained from the Alzheimers Disease Neuroimaging Initiative, an NIH-supported project. Using this method, a specific SNP in the FAM222 gene was identified that was linked to a variety of different patterns of regional brain atrophy.

Upon further investigation, the investigators found evidence that the protein encoded by the gene FAM222A is associated with AD patient-related beta-amyloid plaques, regional brain atrophy, and the protein the team dubbed aggregatinwhich attaches to amyloid beta peptide and accumulates in the center of plaque in AD patients.

Based on the data we have, this protein can be an unrecognized new risk factor for Alzheimers disease (AD), said Xinglong Wang, an associate professor of pathology at the School of Medicine in a press release. We also see this as a potential novel therapeutic target for this devastating disease.

Wang noted that additional research would be required to confirm the function and role aggregatin plays in the development of AD, he is optimistic this discovery could one day lead to clinical trials of targeting the protein. With an eye toward this possibility, Wang, his colleague Xiaofeng Zhu, a professor of Population and Quantitative Health Sciences at the School of Medicine and the research team have filed for a patent via Case Westerns Office of Research and Technology Management for novel Alzheimers disease treatments and diagnosis based on this and related study.

After identifying aggregatin, the research team then injected mouse models with the protein it had made from the FAM222A gene. They discovered that plaque (amyloid deposits) formation accelerated in the brain of the mice injected with aggregatin, resulting in more neuroinflammation and cognitive dysfunction due to the protein binding directly to the amyloid beta peptide, which facilitated aggregation and plaque formation.

Conversely, when the protein was suppressed plaques were reduced and neuroinflammation and cognitive impairment alleviated. Their findings indicate that reducing levels of this protein and inhibition of its interaction with amyloid beta peptide could potentially be therapeuticnot necessarily to prevent Alzheimers but to slow its progression.

Were very excited about this because our study is likely the first systematic work combining the identification from a genome-wide association study of high dimensional brain-imaging data and experimental validation so perfectly in Alzheimers disease, Zhu said.

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Gene and Associated Protein May be Key to Slow Alzheimer's Progression - Clinical OMICs News

Organization crafts genetic testing guidelines to ensure reliability – Japan Today

Amid concerns over gene mutations going undetected due to the variety of medical devices and test reagents in use, a Japanese organization has drawn up guidelines for standard procedures and frameworks to ensure that genetic tests are reliable.

The Japanese Committee for Clinical Laboratory Standards published the guidelines after studying international standards as well as guidelines and articles at home and abroad. The guidelines stipulate what staff are required, the records that need to be kept and the correct way to check instruments and reagents.

JCCLS consists of representatives from companies and academic societies with a focus on disease diagnosis and treatment.

The guidelines also call for hospitals and other medical facilities analyzing test results to compare the results with those from other institutions to ensure precision.

The move comes as an increasing number of people are opting to have their genes checked on being diagnosed with an intractable disease or in order to select an appropriate cancer treatment.

In collaboration with the committee, the Japan Accreditation Board, which evaluates abidance to international standards across various fields, has launched work to recognize institutions that carry out genetic testing in line with the new guidelines.

Accreditation is subject to passing on-site investigations and practical exams.

"Producing a correct result is key to safe, secure medicine," said Hayato Miyachi, a Tokai University professor who is involved in crafting the guidelines. "I believe the guideline will play a major role."

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Organization crafts genetic testing guidelines to ensure reliability - Japan Today