When you first meet her, you wont be able to tell that Ipek Kuzu suffers from a rare genetic disease. The three-year-old plays happily on her own for hours, driving her toy cars and cooking in her pretend kitchen. But shes not well. Shes a little wobbly on her feet and doesnt say much, and if nothing is done, she may die by her mid-20s. Ipek has ataxia-telangiectasia, or A-T, a disease caused by an error in her DNA. It causes the loss of brain cells, along with a high risk of infection and cancer.

Its the sort of problem that makes doctors shake their heads. But Ipeks father, Mehmet, and mother, Tugba, hope shell escape that fate. Thanks in part to the persistence of Mehmet, a programmer at Google, in January she became one of the first handful of US patients to receive a hyper-personalized gene medicine, tailored to treat a unique mutation. The one-person drug, designed for her by a Boston doctor, Timothy Yu, is being called atipeksen, for A-T and Ipek.

To create atipeksen, Yu borrowed from recent biotech successes like gene therapy. Some new drugs, including cancer therapies, treat disease by directly manipulating genetic information inside a patients cells. Now doctors like Yu find they can alter those treatments as if they were digital programs. Change the code, reprogram the drug, and theres a chance of treating many genetic diseases, even those as unusual as Ipeks.

The new strategy could in theory help millions of people living with rare diseases, the vast majority of which are caused by genetic typos and have no treatment. US regulators say last year they fielded more than 80 requests to allow genetic treatments for individuals or very small groups, and that they may take steps to make tailor-made medicines easier to try. New technologies, including custom gene-editing treatments using CRISPR, are coming next.

Where it had taken decades for Ionis to perfect its drug, Yu now set a record: it took only eight months for Yu to make milasen, try it on animals, and convince the US Food and Drug Administration to let him inject it into Milas spine.

I never thought we would be in a position to even contemplate trying to help these patients, says Stanley Crooke, a biotechnology entrepreneur and founder of Ionis Pharmaceuticals, based in Carlsbad, California. Its an astonishing moment.

Antisense drug

Right now, though, insurance companies wont pay for individualized gene drugs, and no company is making them (though some plan to). Only a few patients have ever gotten them, usually after heroic feats of arm-twisting and fundraising. And its no mistake that programmers like Mehmet Kuzu, who works on data privacy, are among the first to pursue individualized drugs. As computer scientists, they get it. This is all code, says Ethan Perlstein, chief scientific officer at the Christopher and Dana Reeve Foundation.

A nonprofit, the A-T Childrens Project, funded most of the cost of designing and making Ipeks drug. For Brad Margus, who created the foundation in 1993 after his two sons were diagnosed with A-T, the change between then and now couldnt be more dramatic. Weve raised so much money, weve funded so much research, but its so frustrating that the biology just kept getting more and more complex, he says. Now, were suddenly presented with this opportunity to just fix the problem at its source.

Ipek was only a few months old when her father began looking for a cure. A geneticist friend sent him a paper describing a possible treatment for her exact form of A-T, and Kuzu flew from Sunnyvale, California, to Los Angeles to meet the scientists behind the research. But they said no one had tried the drug in people: We need many more years to make this happen, they told him.

Courtesy Photo (Yu)

Kuzu didnt have years. After he returned from Los Angeles, Margus handed him a thumb drive with a video of a talk by Yu, a doctor at Boston Childrens Hospital, who described how he planned to treat a young girl with Batten disease (a different neurodegenerative condition) in what press reports would later dub a stunning illustration of personalized genomic medicine. Kuzu realized Yu was using the very same gene technology the Los Angeles scientists had dismissed as a pipe dream.

That technology is called antisense. Inside a cell, DNA encodes information to make proteins. Between the DNA and the protein, though, come messenger molecules called RNA that ferry the gene information out of the nucleus. Think of antisense as mirror-image molecules that stick to specific RNA messages, letter for letter, blocking them from being made into proteins. Its possible to silence a gene this way, and sometimes to overcome errors, too.

Though the first antisense drugs appeared 20 years ago, the concept achieved its first blockbuster success only in 2016. Thats when a drug called nusinersen, made by Ionis, was approved to treat children with spinal muscular atrophy, a genetic disease that would otherwise kill them by their second birthday.

Yu, a specialist in gene sequencing, had not worked with antisense before, but once hed identified the genetic error causing Batten disease in his young patient, Mila Makovec, it became apparent to him he didnt have to stop there. If he knew the gene error, why not create a gene drug? All of a sudden a lightbulb went off, Yu says. Couldnt one try to reverse this? It was such an appealing idea, and such a simple idea, that we basically just found ourselves unable to let that go.

Yu admits it was bold to suggest his idea to Milas mother, Julia Vitarello. But he was not starting from scratch. In a demonstration of how modular biotech drugs may become, he based milasen on the same chemistry backbone as the Ionis drug, except he made Milas particular mutation the genetic target. Where it had taken decades for Ionis to perfect a drug, Yu now set a record: it took only eight months for him to make milasen, try it on animals, and convince the US Food and Drug Administration to let him inject it into Milas spine.

Whats different now is that someone like Tim Yu can develop a drug with no prior familiarity with this technology, says Art Krieg, chief scientific officer at Checkmate Pharmaceuticals, based in Cambridge, Massachusetts.

Source code

As word got out about milasen, Yu heard from more than a hundred families asking for his help. Thats put the Boston doctor in a tough position. Yu has plans to try antisense to treat a dozen kids with different diseases, but he knows its not the right approach for everyone, and hes still learning which diseases might be most amenable. And nothing is ever simpleor cheap. Each new version of a drug can behave differently and requires costly safety tests in animals.

Kuzu had the advantage that the Los Angeles researchers had already shown antisense might work. Whats more, Margus agreed that the A-T Childrens Project would help fund the research. But it wouldnt be fair to make the treatment just for Ipek if the foundation was paying for it. So Margus and Yu decided to test antisense drugs in the cells of three young A-T patients, including Ipek. Whichever kids cells responded best would get picked.

Matthew Monteith

While he waited for the test results, Kuzu raised about $200,000 from friends and coworkers at Google. One day, an email landed in his in-box from another Google employee who was fundraising to help a sick child. As he read it, Kuzu felt a jolt of recognition: his coworker, Jennifer Seth, was also working with Yu.

Seths daughter Lydia was born in December 2018. The baby, with beautiful chubby cheeks, carries a mutation that causes seizures and may lead to severe disabilities. Seths husband Rohan, a well-connected Silicon Valley entrepreneur, refers to the problem as a tiny random mutation in her source code. The Seths have raised more than $2 million, much of it from co-workers.

Custom drug

By then, Yu was ready to give Kuzu the good news: Ipeks cells had responded the best. So last September the family packed up and moved from California to Cambridge, Massachusetts, so Ipek could start getting atipeksen. The toddler got her first dose this January, under general anesthesia, through a lumbar puncture into her spine.

After a year, the Kuzus hope to learn whether or not the drug is helping. Doctors will track her brain volume and measure biomarkers in Ipeks cerebrospinal fluid as a readout of how her disease is progressing. And a team at Johns Hopkins will help compare her movements with those of other kids, both with and without A-T, to observe whether the expected disease symptoms are delayed.

One serious challenge facing gene drugs for individuals is that short of a healing miracle, it may ultimately be impossible to be sure they really work. Thats because the speed with which diseases like A-T progress can vary widely from person to person. Proving a drug is effective, or revealing that its a dud, almost always requires collecting data from many patients, not just one. Its important for parents who are ready to pay anything, try anything, to appreciate that experimental treatments often dont work, says Holly Fernandez Lynch, a lawyer and ethicist at the University of Pennsylvania. There are risks. Trying one could foreclose other options and even hasten death.

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Kuzu says his family weighed the risks and benefits. Since this is the first time for this kind of drug, we were a little scared, he says. But, he concluded, theres nothing else to do. This is the only thing that might give hope to us and the other families.

Another obstacle to ultra-personal drugs is that insurance wont pay for them. And so far, pharmaceutical companies arent interested either. They prioritize drugs that can be sold thousands of times, but as far as anyone knows, Ipek is the only person alive with her exact mutation. That leaves families facing extraordinary financial demands that only the wealthy, lucky, or well connected can meet. Developing Ipeks treatment has already cost $1.9 million, Margus estimates.

Some scientists think agencies such as the US National Institutes of Health should help fund the research, and will press their case at a meeting in Bethesda, Maryland, in April. Help could also come from the Food and Drug Administration, which is developing guidelines that may speed the work of doctors like Yu. The agency will receive updates on Mila and other patients if any of them experience severe side effects.

The FDA is also considering giving doctors more leeway to modify genetic drugs to try in new patients without securing new permissions each time. Peter Marks, director of the FDAs Center for Biologics Evaluation and Research, likens traditional drug manufacturing to factories that mass-produce identical T-shirts. But, he points out, its now possible to order an individual basic T-shirt embroidered with a company logo. So drug manufacturing could become more customized too, Marks believes.

Custom drugs carrying exactly the message a sick kids body needs? If we get there, credit will go to companies like Ionis that developed the new types of gene medicine. But it should also go to the Kuzusand to Brad Margus, Rohan Seth, Julia Vitarello, and all the other parents who are trying save their kids. In doing so, they are turning hyper-personalized medicine into reality.

Erika Check Hayden is director of the science communication program at the University of California, Santa Cruz.

More:
If DNA is like software, can we just fix the code? - MIT Technology Review

For the cell and gene therapy revolution to be fullyrealized, physicians, research scientists, biomanufacturing experts, advocacygroups, regulatory bodies like the Food & Drug Administration (FDA) andother key stakeholders have to Think Different, as Apple famously encouraged.

The vein-to-vein, one batch to one patientformula of personalized medicine is radically and rapidly forcing changes onbiomanufacturing where cell and gene therapy best practices are not yetcalcified and are changing as we speak. Personalized medicine supply chainchallenges are emerging and still being worked through and the high cost ofthese therapies remains a daunting challenge for life science companies andpatients.

Cell and gene therapy challenges across R&D, manufacturing, commercialization, and supply chain as well as bioethical challenges yet to be fully confronted or resolved have been well documented and discussed by experts across the BioHealth Capital Region (BHCR).

One company Jeeva InformaticsSolutions, Inc. (Jeeva) in Herndon, Virginia is developing BigData solutions for a less publicized but equally urgent cell and gene therapychallenge: How to manage a radically new form of clinical trial that could spandecades. Founder and CEO of Jeeva, Harsha K. Rajasimha, is building a companythat leverages Big Data, AI and mobile tech to decentralize clinical trials.Jeevas goal is to make it easier for biotech companies to collect, aggregate,analyze and report required clinical trial data while helping patients stayenrolled and compliant over longer periods of time with little travel from theconvenience of their homes.

The FDA recently passed newindustry guidelines requiring long-term follow up (LTFU) periods ofup to 15 years for gene and cell therapies, representing a sea change for howclinical trials will operate in the future.

The cell and gene therapy space provides significant hope for cures that can reverse genetic mutations. This space is growing. There are more than 900 clinical trials ongoing. Hundreds if not thousands of genetic diseases are likely to have therapies for the first time in our lifetime, stated Rajasimha.

At Jeeva, we are trying to solve a number ofissues but have focused on one particular problem that needs to be addressed ifthese cell and gene therapies are going to be delivered to patients: No oneknows the long term implications of these therapies because they are a one anddone type treatment. If a patient receives therapy today, they are done, and sothe FDA has mandated that recipients need to be monitored for up to 15 years.We are looking to address this issue with digital health technologies and AI,he added.

Jeeva believes that these long-term monitoringchallenges can be managed by making clinical trial participation easier viamobile applications, video conferencing consultations and centralizedscheduling, to name just a few of Jeevas product features. Leveraging digitalhealth tech can reduce the need for travel and eliminate inconveniences thatmight cause a patient to become non-compliant or, worse, drop out of a trialaltogether.

Decentralized clinical trials eliminate the heavy burden of patient travel and makes the process simpler and more efficient. Utilizing a Bring-Your-Own-Device (BYOD) approach and an eVisit consultation model to create decentralized trials can reduce brick and mortar visits by 20% to 80%, according to Jeeva.

Thenew FDA guidelines is the latest attempt to grapple with unchartedsafety protocols for cell and gene therapies. Clinical trial challenges are notnew to the biotechnology industry, however; rather, the approach to clinicaltrials has been inefficient and static for decades, leading to industry-wideproblems with clinical trial enrollment and recruitment that has a dominoeffect that lengthens the commercialization process and increases drugdevelopment costs.

We want to be a catalyst for accelerating thedrug development and delivery process. Patient recruitment is a huge barrierand has made the biopharmaceutical industry unsustainable. The average cost ofbringing a drug to market is $2.5B and takes 10-15 years to get to market. Wefeel that by educating and informing the global community about clinical trialsand enrollment opportunities using AI and digital health tech, we can help allstakeholders in getting people earlier access to treatments and getting thetreatments to markets faster, Rajasimha said.

Jeeva not only can help small to midsize biotechs improve trial recruitment and longer-term safety monitoring, but the company uses AI to improve clinical trial operations. By using AI and high tech tools, biotech companies can leverage historical trial data to shape new trials while empowering real-time adjustments to trials based on real-time monitoring to improve overall success rates.

Rajasimha continued, We have been building AItools to solve our customers specific needs, not just for AIs sake. Wesurveyed our customers last year and they told us Every single clinical trialseems like the first trial ever conducted by mankind. Even companies likePfizer and Novartis, which have been conducting hundreds of trials for decades,feel that when they launch a new trialit is no more efficient than theprevious trial.

So, we have been building an AI assistant that learns from past clinical trials data to make the next trial more efficient, he added. Rajasimha quickly reinforced patient centricity by saying it is not something you fix with an all technology solution, unless the robustly tested technology solution is combined with the human elements and focus on patients perspectives. Having been a global patient advocate in the U.S. over the past six years has given me a unique perspective on how to integrate technology in the lives of patients and caregivers. Moreover, a growing number of trials are recruiting patients from multiple countries and reducing international travel burden on patients over extended durations will be critical to achieve enrollment.

While the concept of virtual clinical trialsmight seem futuristic, Rajasimha and the Jeeva team believe the market is readyfor change.

A number of pilot projects or proof of concept clinical trials, about 20 of them, have been published where patients didnt go to the clinic at all. The feasibility of conducting such remote patients studies has been validated multiple times by the industry now. The tipping point has arrived. One of the key barriers for widespread adoption of decentralized clinical trials was a lack of FDA guidelines. Now the FDA has clarified its expectations about how the industry and stakeholders can share the responsibility to reduce the burden on patients. Enough validation and regulatory guidelines have put us in a position to give our customers what they need, stated Rajasimha.

Rajasimha sees partnering with smaller to midsize biotechs early on in the drug development process meaning well before the start of Phase II or III trials as an inflection point where it can deliver the greatest impact. In addition, we are seeing some initial interest from the Medical Cannabis industry, opioid crisis intervention for chronic pain management, and patient advocacy groups, where patients often live in remote, rural areas, can also benefit from decentralized, hybrid virtual clinical trials. Finally, real-world evidence studies, or longitudinal cohort studies, is also a growing market because companies need to collect and manage patients across longer time horizons, which is Jeevas sweet spot.

Rajasimha and Jeeva are starting to see this growing market interest manifest itself in new funding partnerships. Jeeva recently announced that CIT GAP Funds had invested in the company. Jeeva is currently in an early-stage investment round and the company is in active product development with a validated prototype. Jeeva is seeking new customer pilot projects to add to its ongoing pilots, which include chronic pain, medical cannabis, oncology and cell, and gene therapy products. Later this year, the company plans to complete multiple pilot projects and have validation in Good Clinical Practices (GCP) settings.

Rajasimha and his Jeeva team are certainlyembracing a think different approach to the future of clinical trials. Jeevaand its AI-driven, virtual clinical trial model is poised to help biotechcompanies thrive and meet the unmet medical needs of more patients across theglobe.

You can listen to Rajasimhas interviewwith podcast host Daniel Levine earlier this month on iheart radio here.

Team Jeeva is seeking customer pilot projectsand strategic partners to join the journey and will be exhibiting at the NationalInstitutes of Health Rare Disease Day event on Feb 28, 2020.Rajasimha will also be delivering a keynote speech on AI in rare diseases atthe BIO-IT World West Conference at San Franciscoon March 3rd, 2020.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

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This Startup is on a Mission to Decentralize Cell and Gene Therapy Clinical Trials - BioBuzz

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

A study published in Precision Oncology demonstrates that RNA genetic testing, conducted at the same time as DNA testing, identifies more genetic mutations that increase genetic cancer risk than DNA testing alone.[1]

The results of the study shows the first notable improvement in diagnostic yield for high-risk cancer genes in more than 10 years.

Using +RNAinsight, Ambry Genetics, a division of Konica Minolta Precision Medicine, is the first laboratory offering concurrent RNA and DNA genetic testing for hereditary cancer risk as a commercially available clinical test.

+RNAinsight, paired with Ambry Genetics hereditary cancer DNA tests, uses next-generation sequencing to concurrently analyze a patients DNA and RNA. This approach not only improves the sensitivity and clarity of genetic testing, it works in tandem with DNA testing to identify patients with or at-risk for hereditary cancer who might otherwise be missed, decrease variants of unknown significance (VUS) in real-time, and provide more accurate results to inform patient care.[2]

Mutations, Variants or errorsOverall, more than 50 hereditary cancer syndromes have been described. Most of these cancers are caused by harmful mutations, also known as variants or errors, that are inherited in an autosomal dominant fashion in which a single altered copy of a gene inherited from one parent is enough to increase a persons chance of developing cancer. In addition, a number of tests screen for inherited genetic variants that are not associated with named syndromes but have been found to increase cancer risk. This, for example, includes inherited variants in PALB2, which is associated with increased risks of breast and pancreatic cancers, CHEK2, associated with breast and colorectal cancers, BRIP1, RAD51C and RAD51D, associated with ovarian cancer.[3]

Overall, these mutations in our DNA increase cancer risk, play a major role in about 5% 10% of all cancers. Genetic testing identifies these inherited mutations and is a critical tool to prevent hereditary cancers or treat them early.

However, standard DNA testing for hereditary cancer risk excludes portions of DNA, and, as a result, misses some mutations. In addition, DNA testing can produce inconclusive results and fail to determine whether a variant increases cancer risk.

These limitations impact patients and their families because doctors may not have the information needed to recommend appropriate preventive, early-detection, or therapeutic steps. Furthermore, relatives may not be referred for genetic testing and obtain the care they would otherwise have gotten if they had learned they had certain mutations.

RNA genetic testingAdding RNA genetic testing at the same time as DNA testing helps address these limitations. Specifically, RNA genetic testing is an additional line of evidence that helps determine that an uncertain result from DNA-only testing is either benign or pathogenic.

In addition, RNA generic testing also helps identify mutations that DNA-only testing misses.

In the study published Precision Oncology, the authors describe their scalable and targeted approach to RNA genetic testing that is performed concurrently with DNA genetic testing, demonstrating such an approach that identified more mutations than DNA-only testing.

Working together with 19 other leading clinical institutions across the United States, including Mass General Cancer Center, Huntsman Cancer Institute, and the Perelman School of Medicine at the University of Pennsylvania, researchers at Ambry Genetics looked at 18 tumor suppressor genes where the loss of function is known to be associated with increased cancer. Their work resulted in a prospective study on the first 1,000 patients sent in for hereditary cancer testing using RNA testing coupled with DNA.

The study found that RNA testing identified seven patients with pathogenic mutations that would otherwise have received negative or inconclusive results on DNA testing alone. For six of these seven cases, substantial changes to medical management could be or were recommended based on current guidelines.

FeasibilityThe study findings demonstrate both the feasibility and clinical utility of adding concurrent RNA genetic testing to determine hereditary cancer risk, said Tyler Landrith, Ph.D., an Ambry scientist, and study co-author.

[Our] +RNAinsight provides healthcare providers with more accurate results to inform patient care, Landrith added.

Relative increaseThe prospective analysis showed a 9.1% relative increase in diagnostic yield than DNA testing alone. Adding RNA genetic testing also resulted in a 5.1% relative decrease in the number of patients that otherwise would have received inconclusive results with DNA testing alone and would not have learned whether they had increased cancer risk.

Paired RNA and DNA genetic testing have given answers to my patients who have struggled for years with inconclusive results that left them feeling helpless, said Community Health Network Genetic Counselor Rebekah Krukenberg.

With +RNAinsight, I know that Im providing my patients with the most accurate and conclusive information about their risks for hereditary cancer, she explained.

AccuracyThe study also validated the accuracy of +RNAinsight, establishing a large control dataset of healthy patients. This dataset allowed study authors to establish a baseline for benign and disease-causing variants across the genes tested.

Previous studies have demonstrated the benefits of RNA genetic testing. However, testing has been traditionally performed as a follow-up to inconclusive DNA testing. This approach to RNA testing has limitations that Ambry Genetics +RNAinsight does not have.

Testing at the same timeA previous study showed that only 10% percent of patients invited to receive RNA testing after having undergone DNA testing actually sent in samples. Moreover, retrospective RNA testing only looks at targeted variants and not a full range of possible mutations. Given these limitations, +RNAinsight is made available to all patients at the same time as DNA testing.[4]

Reference[1] Landrith, T., Li, B., Cass, A.A. et al. Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes. npj Precis. Onc. 4, 4 (2020). https://www.nature.com/articles/s41698-020-0109-y%5B2%5D Karam R., Krempelyl K, Richardson ME, McGoIdrickl K, Zimmermann H, Connerl B, Landrithl T, et al., RNA Genetic Testing in Hereditary Cancer Improves Variant Classification and Patient Management. Annual Clinical Genetics Meeting (ACMG) 2019 [Poster][3] Cancer Causes and prevention. Genetic Testing for Inherited Cancer Susceptibility Syndromes. What genetic tests are available for cancer risk assessment? National Cancer Institute. Online Last accesses February 24, 2020.[4] Karam R, Conner B, LaDuca H, McGoldrick K, Krempely K, Richardson ME, Zimmermann H, et al. Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer. JAMA Netw Open. 2019;2(10):e1913900. doi:10.1001/jamanetworkopen.2019.13900 [Article]

Excerpt from:
+RNAinsight Identifies More Patients with Increased Hereditary Cancer Risk vs. DNA-only Test - OncoZine

Manipulating cellular metabolism may provide a promising therapeutic intervention in autoimmune diseases.

Laurie Harrington, Ph.D.Patients with autoimmune diseases like multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis have an imbalance between two types of immune system T cells. Destructive Th17 cells that mediate chronic inflammation are elevated, and regulatory T cells, or Treg cells, which suppress inflammatory responses and play a protective role in autoimmune disorders, are diminished.

Both cells differentiate from the same precursors nave CD4 T cells and the beginning of their change to either Th17 or Treg cells starts with the same signal. Subsequently, a fate decision occurs, like a fork in the road, steering the changing CD4 cells to become either inflammatory T cells or regulatory T cells.

New, preclinical research, led by Laurie Harrington, Ph.D., associate professor in the UAB Department of Cell, Developmental and Integrative Biology at the University of Alabama at Birmingham, shows a pivotal role for cellular metabolism to regulate that fate decision, a decision that occurs very early in the activation of CD4 T cells. This opens a possibility that manipulating the cellular metabolism of T cells may provide a new, promising therapeutic intervention to modulate the balance between pathogenic Th17 and Treg cells in chronic autoimmune disorders. The research is published in the journal Cell Reports.

Upon activation, T cells were known to rapidly increase metabolism, including glycolysis and mitochondrial oxidative phosphorylation, or OXPHOS, to meet the energetic demands of differentiation. But the precise contribution of OXPHOS to that Th17 differentiation was not defined.

The UAB researchers, and one colleague at New York University, found that ATP-linked mitochondrial respiration during Th17 differentiation was essential to upregulate glycolysis and the TCA cycle metabolism. Strikingly, it also was essential to promote inflammation of the central nervous system by Th17, as shown in a mouse model for multiple sclerosis.

In the mouse model, experimental autoimmune encephalitis, Th17 cells cause the disease progression. For the experiment, harvested CD4 T cells were differentiated using a combination of Th17-polarizing cytokines. One group was the polarized control, and one group was polarized in the presence of oligomycin, an inhibitor of mitochondrial OXPHOS. Then the T cells were transferred into experimental mice. Mice receiving the T cells treated with oligomycin during polarizing conditions showed a significantly delayed onset of disease and reduced disease severity. Both groups of T cells proliferated robustly after transfer.

In mechanistic experiments, the researchers detailed the early molecular events that differ between cells polarized in the presence or absence of oligomycin. These included gene sets that are upregulated or downregulated, presence or absence of Th17 or Treg cell markers, expression of signature transcription factors needed for Th17 differentiation, and expression of gene products that play a role in T cell receptor signaling.

A surprise was found in the timing of the fate decision. In an experiment, CD4 T cells were exposed to Th17-polarizing conditions with oligomycin present only during the first 24 hours. They were then washed and allowed to continue differentiation in the polarizing conditions. The effects of this brief exposure to oligomycin were T cells that lacked Th17 markers and instead showed hallmarks of Treg cells, including expression of Foxp3. Thus, the brief early exposure to oligomycin imprinted the Foxp3 fate decision.

Overall, Harrington said, inhibition of mitochondrial OXPHOS ablates Th17 pathogenicity in a mouse model of multiple sclerosis and results in generation of functionally suppressive Treg cells under Th17 conditions.

Co-authors with Harrington of the study, Mitochondrial oxidative phosphorylation regulates the fate decision between pathogenic Th17 and regulatory T cells, are Boyoung Shin, UAB Department of Cell, Developmental and Integrative Biology; Gloria A. Benavides and Victor M. Darley-Usmar, UAB Department of Pathology; Jianlin Geng and Hui Hu, UAB Department of Microbiology; and Sergei B. Koralov, New York University Grossman School of Medicine.

Support came from National Institutes of Health grants AI113007 and DK079337, American

Heart Association grant 16PRE29650004, an AMC21 Award from the UAB School of Medicine, and a Blue Sky Award from the UAB School of Medicine.

At UAB, Darley-Usmar holds the Endowed Professorship in Mitochondrial Medicine and Pathology.

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Cellular metabolism regulates the fate decision between pathogenic and regulatory T cells - UAB News

Some 100,000 Americans are placed on kidney dialysis and the transplant list every year in the U.S.

Rich Pedroncelli | AP

Medical experts are hoping 2020 will mark a turning point in the fight against kidney disease in America, thanks to advancing technology. Currently, the U.S. spends about $100 billion annually to treat the nearly 40 million Americans suffering from chronic kidney disease who need dialysis and organ transplants. The public health crisis, exacerbated by the rise in obesity and type 2 diabetes, is now the ninth leading cause of death in the nation, according to the Centers for Disease Control and Prevention.

President Donald Trump'sAdvancing American Kidney Health Initiative, launched in July, was a nod that this is one area of medicine in urgent need of innovation. The new plan calls for the CDC to improve kidney disease tracking and detection nationwide. It also calls for a change in Medicare provider payment models to prioritize preventive care from doctors, develop effective home-care dialysis and find ways to boost organ supply including encouraging the development of an artificial kidney.

President Donald Trump displays an executive order he has just signed during an event on kidney health at the Ronald Reagan Building and International Trade Center on July 10, 2019, in Washington, DC.

Alex Wong | Getty Images

One company making inroads in the field is RenalytixAI, an AI clinical diagnostics company for kidney disease. It has received an FDA breakthrough device designation for its KidneyIntelX, an AI-powered diagnostic product for kidney disease that is expected to launch in the second quarter of this year in the U.S.

The diagnostic developed in collaboration with the Mount Sinai Health System in New York City, which has 3 million patient health records and 52,000 biobank participants uses machine learning algorithms to assess the combination of blood-based biomarkers and electronic health records information and other genomic information to identify progressive kidney disease in patients. From this collection of data, the company aims to build new models to predict kidney disease progression and how a given patient might respond to a treatment.

In addition, it has developed FractalDX, a lab-based AI tool that can predict the risk of adverse transplant outcomes, including early kidney rejection.

"This is an epidemic, and it is a silent killer, since symptoms don't appear until the disease is in the final stages and a patient needs dialysis and transplantation," says James McCullough, CEO of RenalytixAI. "Just look at the numbers they are staggering. Some 100,000 Americans get put on kidney dialysis and the transplant list each year."

Despite the rising trend, there is an organ donor shortage in the U.S. Last year there were only about 21,000 donor organs available for transplant, according to The Kidney Project, at the University of California in San Francisco.

As a result, reveals data from Mount Sinai, 23% of people on kidney dialysis die every year.

Kidney transplant surgery.

BSIP | Universal Images Group | Getty Images

"Unfortunately, the disease is disproportionately hitting African and Hispanic Americans for two reasons," points out Dr. Girish Nadkarni, co-founder of RenalytixAI and an assistant professor of nephrology at Mount Sinai. "Many people in these populations have a genetic mutation of the APOL1 gene. In addition, because of socioeconomics, many don't have access to healthy food, and other poor socioeconomic conditions."

This is an epidemic, and it is a silent killer, since symptoms don't appear until the disease is in the final stages and a patient needs dialysis and transplantation.

James McCullough

CEO of RenalytixAI

Recognizing this problem, the Centers for Medicare and Medicaid Services has set a national price and reimbursement code for the KidneyIntelX test at $950, effective until December 2022, and the American Medical Association has provided a CPT reimbursement code. This should accelerate private insurers to provide coverage for the test.

Dr. Chirag Parikh, chief of nephrology at Johns Hopkins and a board member of RenalytixAI, is excited by the prospects of the new technology and other innovations in the field that are beginning to bubble up in the community. "In my 25-year career, I have never seen such a confluence of factors converging to bring about advances in the field." He pointed to public-private partnerships such as the KidneyX incubator a partnership between HHS and the American Society of Nephrology that's trying to reinvent kidney dialysis treatment.

Globally, kidney disease affects more than 850 million people, making its early detection crucial. It's a huge market that needs disruption, and companies such as Google are looking at finding ways to use AI to tackle the problem.

Last yearDeepMind, now part of Google Health, unveiled an algorithm that predicts acute kidney injuries in patients who would end up needing dialysis 48 hours before many symptoms can be recognized by doctors. The work was the result of a project with the U.S. Department of Veteran Affairs.

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A major breakthrough for the millions of Americans on the brink of kidney failure and dialysis - CNBC

ONPATTRO is the First-Ever RNAi Therapeutic Approved in Latin America

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the Brazilian Health Regulatory Agency (ANVISA) has approved ONPATTRO (patisiran) for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in adults with stage 1 or stage 2 polyneuropathy. hATTR amyloidosis is a rare, progressive condition that is considered endemic in Brazil, affecting more than 5,000 people.i Based on Nobel Prize-winning science, ONPATTRO is the first approved RNAi therapeutic in Latin America and will be the first Alnylam product launched and marketed in the region.

"The approval of ONPATTRO in Brazil marks an exciting milestone for so many Brazilians with hATTR amyloidosis in need of a new treatment option that could halt the progression of this debilitating and life-threatening disease. We are grateful to ANVISA for recognizing the significant impact of this disease on patients daily lives and for granting approval to the first RNAi therapeutic in Latin America ONPATTRO so swiftly, a mere four months after the marketing authorization application was filed. We will continue collaborating with ANVISA and the Ministry of Health in order to incorporate ONPATTRO in the federal program (SUS), to make the drug available to patients in need as soon as possible," said Norton Oliveira, Senior Vice President, Head of Latin America at Alnylam.

ONPATTROs approval is based on positive data from the APOLLO Phase 3 study, which evaluated the efficacy and safety of patisiran in hATTR amyloidosis patients with polyneuropathy. Results from the APOLLO study were published in the July 5, 2018 issue of The New England Journal of Medicine.

ANVISA granted ONPATTRO priority review, an accelerated review designation awarded to innovative medicines that treat rare diseases. ONPATTRO has previously been approved for use in the U.S., EU, Canada, Japan, and Switzerland. The therapy had been granted Breakthrough Therapy and Orphan Drug designation by the U.S. Food and Drug Administration, along with priority or accelerated review status from regulatory agencies in the U.S., EU, Canada, and Japan.

About ONPATTRO (patisiran)

ONPATTRO is an RNAi therapeutic that was approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. Based on Nobel Prize-winning science, ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made. ONPATTRO blocks the production of TTR in the liver, reducing its accumulation in the bodys tissues in order to halt or slow down the progression of the polyneuropathy associated with the disease. For more information about ONPATTRO, visit ONPATTRO.com.

ONPATTRO Important Safety Information

Infusion-Related Reactions

Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In a controlled clinical study, 19 percent of ONPATTRO-treated patients experienced IRRs, compared to 9 percent of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache. To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation

ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.

Story continues

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions

The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory-tract infections (29 percent) and infusion-related reactions (19 percent).

For additional information about ONPATTRO, please see the full Prescribing Information.

About hATTR Amyloidosis

Hereditary transthyretin (TTR)-mediated amyloidosis (hATTR) is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. TTR protein is primarily produced in the liver and is normally a carrier of vitamin A. Mutations in the TTR gene cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. hATTR amyloidosis, represents a major unmet medical need with significant morbidity and mortality affecting approximately 50,000 people worldwide. The median survival is 4.7 years following diagnosis, with a reduced survival (3.4 years) for patients presenting with cardiomyopathy.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of todays medicines by potently silencing messenger RNA (mRNA) the genetic precursors that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam

Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylams commercial RNAi therapeutic products are ONPATTRO (patisiran), approved in the U.S., EU, Canada, Japan, and Switzerland, and Brazil, and GIVLAARI (givosiran), approved in the U.S. Alnylam has a deep pipeline of investigational medicines, including five product candidates that are in late-stage development. Alnylam is executing on its "Alnylam 2020" strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam employs over 1,300 people worldwide and is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit http://www.alnylam.com and engage with us on Twitter at @Alnylam or on LinkedIn.

Alnylam Forward Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam's views and plans with respect to the potential for RNAi therapeutics, including ONPATTRO, its plans for the launch of ONPATTRO in Brazil and continuing product launches globally, and expectations regarding the continued execution on its "Alnylam 2020" guidance for the advancement and commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all; actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; intellectual property matters including potential patent litigation relating to its platform, products or product candidates; obtaining regulatory approval for its product candidates, including lumasiran, and maintaining regulatory approval and obtaining pricing and reimbursement for its products, including ONPATTRO and GIVLAARI; progress in continuing to establish a commercial and ex-United States infrastructure, including in Brazil; successfully launching, marketing and selling its approved products globally, including ONPATTRO and GIVLAARI, and achieve net product revenues for ONPATTRO within our expected range during 2020; Alnylams ability to successfully expand the indication for ONPATTRO in the future; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's ability to manage its growth and operating expenses within the ranges of its expected guidance and achieve a self-sustainable financial profile in the future, obtain additional funding to support its business activities, and establish and maintain strategic business alliances and new business initiatives; Alnylam's dependence on third parties, including Regeneron, for development, manufacture and distribution of certain products, including eye and CNS products, and Ironwood, for assistance with the education about and promotion of GIVLAARI; the outcome of litigation; the risk of government investigations; and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

i Pinto MV et al. Arq Neuropsiquiatr. 2018;76(9):609-621

View source version on businesswire.com: https://www.businesswire.com/news/home/20200226005457/en/

Contacts

Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom (Investors and Media) 617-682-4340

Joshua Brodsky (Investors) 617-551-8276

Continued here:
Alnylam Announces Approval in Brazil of ONPATTRO for the Treatment of Hereditary ATTR Amyloidosis with Polyneuropathy - Yahoo Finance

Elber Yuksel Aydin, 1, 2 Andrea Schneider, 1, 3 Dragana Protic, 1, 4 Jun Yi Wang, 1, 5 Veronica Martnez-Cerdeo, 1, 6 Flora Tassone, 1, 7 Hiu-Tung Tang, 7 Susan Perlman, 8 Randi J Hagerman 1, 3

1Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA, USA; 2Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; 3Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA, USA; 4Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia; 5Center for Mind and Brain, University of California Davis School of Medicine, Sacramento, CA, USA; 6Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine, University of California Davis School of Medicine and Shriners Hospital, Sacramento, CA, USA; 7Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA, USA; 8Department of Neurology, University of California Los Angeles School of Medicine, Los Angeles, CA, USA

Correspondence: Randi J HagermanMIND Institute UCDMC, 2825 50th Street, Sacramento, CA 95817, USAEmail rjhagerman@ucdavis.edu

Abstract: Fragile Xassociated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that usually begins in the early 60s and affects carriers of premutation expansion (55 200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Additional disorders can co-occur with FXTAS including Alzheimers disease (AD). Here we discuss a case report of a male with 67 CGG repeats in FMR1 who had mild late-onset FXTAS symptoms followed by neurocognitive disorder symptoms consistent with AD. The patient has developed tremor and ataxia that are the two characteristic symptoms of FXTAS. In addition, he shows rapid cognitive decline, brain atrophy most substantial in the medial temporal lobe, and decreased metabolism in the brain regions that are the characteristic findings of AD. The purpose of this study is to describe a patient profile with both diseases and review the details of an overlap between these two diseases.

Keywords: FXTAS, Alzheimers disease, cognitive decline, neurocognitive disorder, premutation, neurogenetics

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Excerpt from:
Rapidly Progressing Neurocognitive Disorder in a Male with FXTAS and A | CIA - Dove Medical Press

Xiao-Min Wu,1,* Cheng Jin,2,* Yuan-Long Gu,2 Wu-Qiang Chen,2 Mao-Qun Zhu,2 Shuo Zhang,2 Zhen Zhang1

1Department of Integrated Traditional Chinese and Western Medicine Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, Peoples Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214041, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Cheng JinDepartment of Hepatobiliary Surgery, Affiliated Hospital of Jiangnan University, 585 Xingyuan Road, Wuxi, Peoples Republic of ChinaTel +8613338770679Email jingcheng1008@163.com

Purpose: Hepatocellular carcinoma (HCC) is one of the deadliest cancers globally with a poor prognosis. Breakthroughs in the treatment of HCC are urgently needed. This study explored the role of IDNK in the development and progression of HCC.Methods: IDNK expression was suppressed using short hairpin (shRNA) in BEL-7404 and Huh-7 cells. The expression of IDNK in HCC cells after IDNK knockdown was evaluated by real-time quantitative RT-PCR analysis and Western blot. After IDNK silencing, the proliferation and apoptosis of HCC cells were evaluated by Celigo cell counting, flow cytometry analysis, MTT assay, and caspase3/7 assay. Gene expressions in BEL-7404 cells transfected with IDNK shRNA lentivirus plasmid and blank control plasmid were evaluated by microarray analysis. The differentially expressed genes induced by deregulation of IDNKwere identified, followed by pathway analysis.Results: The expression of IDNK at the mRNA and protein levels was considerably reduced in shRNA IDNK transfected cells. Knockdown of IDNK significantly inhibited HCC cell proliferation and increased cell apoptosis. A total of 1196 genes (585 upregulated and 611 downregulated) were differentially expressed in IDNK knockdown BEL-7404 cells. The pathway of tRNA charging with Z-score = 3 was significantly inhibited in BEL-7404 cells with IDNK knockdown.Conclusion: IDNK plays a key role in the proliferation and apoptosis of HCC cells. IDNK may be a candidate therapeutic target for HCC.

Keywords: hepatocellular carcinoma cells, shRNA IDNK, cell proliferation, cell apoptosis, microarray, differentially expressed gene

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Gluconokinase IDNK Promotes Cell Proliferation and Inhibits Apoptosis | OTT - Dove Medical Press

(WKBW) New York Governor Andrew Cuomo is proposing a new tool in the fight against Alzheimer's. It's called "SUNY Curing Alzheimer's Health Consortium." Cuomo wants to spend five years mapping one million people both suffering from and at-risk of developing the disease.

"And then we will work with SUNY's research institutions, as well as our other research institutions across the state to develop treatments and therapies," Elizabeth Garvey, Special Counsel and Senior Advisor to Governor Cuomo, said.

Empire State Development life science initiative will lend $20 million in funding to recruit 200,000 people for phase one.

"This looks to be a very ambitious program, but one that is very complimentary to the other programs," Dr. Bruce Troen said. He is Chief of the Division of Geriatrics and Palliative Medicine, as well as the Director of Centers of Excellence for Alzheimer's Disease both at Jacobs School of Medicine and Biomedical Sciences. He also works at the Buffalo VA Medical Center.

"Hopefully this will law the foundation for ongoing investigation," he said. Dr. Troen said this proposal is just a piece of the bigger pie. It's not an immediate answer or a cure.

"New York state in taking the lead has been really doing this at a clinical services standpoint, but now it's helping to plant a stake in the ground to say they also want to support research," he said. Gene mapping can play an important role in determining risk factors. The Governor's Office said at the end of this consortium, the data base will be free to use for further research.

"Knowledge is king here...anticipation and prevention is going to help us," he said.

If approved, the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo will participate.

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Fight against Alzheimer's: Governor's proposal would map genes of one million - WKBW-TV