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Genetic counseling field to rapidly expand – CNBC

As a college student at the University of Mount Union in Alliance, Ohio, Megan McMinn studied biology, hoping to one day become a physician’s assistant.

But a desire to interact even more with patients led her down a different path in genetic counseling.

“What genetic counseling gave me was a good split between patient care and the hard science research end of things,” McMinn said.

At Geisinger Health System in Danville, Pa., McMinn sees about six patients a day, working in oncology. Soon, she’ll move onto a cardiology clinic, helping to identify genetic risks for individuals and potentially their families. The system currently has 25 genetic counselors on staff, but anticipates needing hundreds more as genetic testing becomes cheaper and more accessible.

The trend extends far beyond Geisinger, as the field has grown dramatically in the past decade, touching all aspects of health-care as medicine becomes more personalized.

“Genetics permeates everythingthere won’t be enough genetic counselors to see every patient who gets genetic information,” said Mary Freivogel, president of the National Society of Genetic Counselors (NSGC).

As a result, the Bureau of Labor Statistics projects the occupation will grow by 29 percent through 2024, faster than the average for all occupations

“I think [a genetic counselor] will become a key member of the team, discussing with patients and families what to do next, how to figure out how the genome is going to interact with your lifestyle and make decisions about what you want to do medically,” said Dr. David Feinberg, president and CEO of Geisinger Health System.

Genetic counselors typically receive a bachelor’s degree in biology, social science or a related field, and then go on to receive specialized training. Master’s degrees in genetic counseling are offered by programs accredited by the Accreditation Council for Genetic Counseling, offered at some 30 schools in the U.S. and Canada, according to the NSGC.

Those who want to be certified as genetic counselors must obtain a master’s degree from an accredited program, but do not need to be doctors.

The NSGC is also working to recruit new talent by doing outreach in middle and high schools to let younger students know the field is an option in the future. Pay is competitive as wellon average, counselors make around $80,000 a year, but that can increase up to $250,000 annually depending on specialty, location and expertise, Freivogel said.

Health insurance often pays for genetic counseling, and for genetic testing when recommended by a counselor or doctor. However, it’s important to check with insurers before scheduling any tests as coverage levels vary. Cost also varies greatly, for example, as multi-gene cancer panels can range from $300 to $4,000 depending on the type of test, the lab used and whether the patient goes through his or her insurance or pays out of pocket.

And while at-home tests like 23andMe are typically less expensive, those taking them still need to see a genetic counselor to explain their results.

Part of the reason more counselors will be needed in the future at Geisinger is because the health system is home to the MyCode Community Health Initiative, one of the largest biobanks of human DNA samples of its kind, according to Amy Sturm, director of Cardiovascular Genomic Counseling at Geisinger. The project has consent from more than 150,000 patients to participate in having their entire DNA code sequenced and synced with their electronic medical records, to look for new causes of disease and different ways to treat conditions.

“We are figuring out and researching the best way to deliver this information back to our patients and also back to families with the ultimate goal of preventing disease and improving the healthcare system,” Sturm said.

Keeping up with the latest in genomics, where new developments happen almost daily, can be a challenge. Yet counselors like McMinn say the ability to impact more than just the patient by studying the genome makes the job well worth it.

“We are able to bring to the forefront the fact that we’re not just taking care of the patient, but we’re taking care of the entire family,” McMinn said.

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Genetic counseling field to rapidly expand – CNBC

TB: Genetic drug resistance tests as good in gauging treatment outcome, death risk as traditional culture-based tests – Medical Xpress

August 3, 2017 This photomicrograph reveals Mycobacterium tuberculosis bacteria using acid-fast Ziehl-Neelsen stain; Magnified 1000 X. The acid-fast stains depend on the ability of mycobacteria to retain dye when treated with mineral acid or an acid-alcohol solution such as the Ziehl-Neelsen, or the Kinyoun stains that are carbolfuchsin methods specific for M. tuberculosis. Credit: public domain

Novel molecular tests are gaining popularity as a rapid way to detect genetic mutations that render tuberculosis impervious to drugs. Yet, how well these new tests fare in gauging risk of actual drug failure and patient death has remained unclear.

Now research led by scientists at Harvard Medical School reveals that when it comes to predicting response to treatment and risk of dying, molecular tests that detect resistance to a class of TB drugs known as fluoroquinolones may be as good and even superior to traditional drug-sensitivity tests conducted in lab cultures.

The findings of the research are published Aug. 3 in Clinical Infectious Diseases.

Traditional drug-sensitivity testswhich involve exposing a bacterial strain to a series of drugs to determine which medications the bacterium responds tocan take up to eight weeks to yield results. By comparison, point-of-care molecular tests provide results within hours, expediting treatment decisions. However, while these tests can reveal the presence of a genetic mutation within hours, their predictive accuracy in terms of treatment outcomes has not been well established. Past research has indicated that molecular tests may fail to detect resistance mutations in more than 30 percent of strains insensitive to the drug moxifloxacin, which has fueled anxiety about their reliability as resistance detectors.

“Culture-based testing is still considered the gold standard for diagnosing TB resistance,” said study lead investigator Maha Farhat, assistant professor of biomedical informatics at Harvard Medical School and a pulmonary expert at Massachusetts General Hospital.

“However, our results should provide reassuring evidence that molecular tests, which are faster in detecting resistance mutations, are just as reliable, if not better, in predicting overall treatment outcome as a result of such resistance-causing gene alterations in patients who fail treatment with fluoroquinolones.”

The researchers caution their study was relatively small171 patientsand further research is needed to tease out the predictive accuracy of molecular versus standard lab tests in other forms of drug-resistant TB. However, they researchers added, the data provide compelling early evidence that molecular tests could soon become a mainstayand a much faster alternative to traditional testingin informing drug choice and predicting the clinical course of a patient’s infection.

“Widespread implementation of molecular tests to guide regimen development is critical to stemming transmission ofand illness and death due todrug-resistant forms of tuberculosis,” said Carole Mitnick, study senior investigator and associate professor of global health and social medicine at Harvard Medical School. “Our findings also affirm the importance that patients with fluoroquinolone-resistant TBwhether it’s detected by molecular or culture-based testsneed drug regimens that reflect that diagnosis.”

Using cough secretion samples from 171 patients in Lima, Peru, diagnosed with drug-resistant TB and receiving individualized treatment regiments, researchers compared the performance of molecular tests against traditional culture-based testing in detecting resistance to fluoroquinolones, a class of drugs critical for treating multidrug and extensively drug-resistant forms of the disease. Multi-drug resistant TB is defined as disease that does not respond to at least two of the first-line drugs used to treat the infection. Extensively drug-resistant TB is infection that fails to respond to first-line therapies and drugs used as second-line of defense.

Of the 171 samples, 44 carried a genetic mutation known to render TB resistant to one of several fluoroquinolone drugs. Researchers analyzed two types of genetic mutations that lend TB resistant to fluoroquinolonehigh-resistance gene variants as well as gene variants with intermediate level of resistance. Patients whose TB strains harbored the high-resistance mutations were three times more likely to respond poorly to treatment and succumb to the disease than patients whose TB showed no resistance-causing mutations. There were no meaningful differences in outcomes between patients with intermediate mutations and those with none, the analysis showed.

There were no appreciable differences in the chance for treatment failure or death based on the type of test used to detect drug resistance. In other words, the researchers said, patients in whom drug resistance was detected by a molecular test faced similar odds of treatment outcome and death risk as did patients in whom drug resistance was detected via traditional drug-sensitivity testing.

Next, researchers compared how well molecular fared in the context of specific medications within the fluoroquinolone family.

Molecular sequencing outperformed standard drug-sensitivity testing among patients whose disease was resistant to ciprofloxacin. Molecular sequencing was an equally accurate predictor of treatment failure for two other fluoroquinolone drugslevofloxacin and moxifloxacin.

To eliminate the chance that factors other than the type of test being used would influence the results, the researchers also analyzed individual patient treatment regimens, disease severity, the presence of other diseases, smoking and nutritional status, and previous TB treatment, among other characteristics.

Explore further: HIV patients showing signs of multidrug resistance in Africa

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TB: Genetic drug resistance tests as good in gauging treatment outcome, death risk as traditional culture-based tests – Medical Xpress

Genetic Medicine Co. Raises $83.5M For Drug Development – Law360 (subscription)

By Matthew Guarnaccia

Led by Deerfield Management, investors for Homology Medicines Inc.’s Series B funding included Fidelity Management and Research Co., HBM Healthcare Investments, Novartis AG, Vivo Capital and Rock Springs Capital. In addition to Deerfield, 5AM Ventures, ARCH Venture Partners and Temasek Holdings also returned from the companys first round in 2016.

Bedford, Massachusetts-based…

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Genetic Medicine Co. Raises $83.5M For Drug Development – Law360 (subscription)

Gene Editing Is Revolutionizing Medicine but Causing a Government Ethics Nightmare – Newsweek

Updated | Late last week, reports emerged that scientists in Oregon had used gene-editing technology, known as CRISPR-Cas9, to edit a human embryo. While research like this is already occurring in China and Great Britain, this is the first time scientists in the U.S. have edited an embryo.

The move raises thequestion of whether regulations are strict enough in the U.S. Both Congress and the National Institutes of Health have explicitly said they would not fund research that uses gene-editing to alter embryos. But laws and guidelines are not keeping pace with this fast-moving and controversial work.

CRISPR is an experimental biomedical technique in which scientists are able to alter DNA, such as change the misspellings of a gene that contributes to mutations. The technology has the potential to reverse and eradicate congenital diseases if it can be used successfully on a developing fetus.

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Here’s how CRISPR gene editing works. REUTERS

The news frenzy that followed this announcement was based on a leak from unknown sources. Initial reports emerged from a number of less known sources, including MIT Technology Review, that Shoukhrat Mitalipov of Oregon Health and Science University used the technology to change the DNA of not just one, but a number of embryos. But the news stories about this research werent based on a published study, which means they dont provide the full picture. No one yet knows what the researchers did or what the results were.

Until now, most of the breakthrough research on CRISPRaside from the discovery itself, which is attributed to multiple research groups in the U.S. has occurred in China. InApril 2015, Chinese scientists reported that theyd edited the genome of human embryos, a world first, in an attempt to eliminate the underlying cause of a rare blood disorder.

Researchers there have also been experimenting with CRISPR technology to treat cancer. Last spring, a team of scientists at Sichuan Universitys West China Hospital used the approach to modify immune cells in a patient with an aggressive form of lung cancer. The researchers altered genes in a bid to empower the cells to combat the malignancy. Another group of Chinese scientists tried changing genes in blood that were then injected into a patient with a rare form of head and neck cancer to suppress tumor growth.

Despite potential of CRISPR to cure fatal diseases, the technology has fast become one of the most significant challenges for bioethicists. Some people view its power as potentially dangerous because it could allow scientists to cherry-pick genetic traits to create so-called designer babies.

Arthur Caplan, a professor of bioethics at New York University’s Langone Medical Center and founding director of NYULMC’s division of medical ethics thinks the fears are overblown. Gene-editing technology, says Caplan, is nowhere near this sci-fi fantasy.

If you would compare this to a trip to Mars, you’re basically launching some satellites, says Caplan. He suggests that much of the media coverage on CRISPR is melodramatic, including last weeks coverage of researchers meddling with an embryo. We haven’t shown that you can fix a disease or make someone smarter.

Lack of Guidelines

CRISPR technology isnt ready for clinical use, whether to stop serious genetic diseases or simply make brown eyes blue. But geneticists are working toward these goals, and the scientific community is ill-prepared to regulate this potentially powerful technology.

So far guidelines for using CRISPR are minimal. In 2015, the National Institutes of Health issued a firm statement. Advances in technology have given us an elegant new way of carrying out genome editing, but the strong arguments against engaging in this activity remain, the NIH said in its statement. These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos.

But although the NIH wont back CRISPR research for embryo editing, that doesnt mean such research is prohibited in the U.S. Private organizations and donors fund researchers. Caplan suspects this is how the team in Oregon managed to carry out their experiment.

In February 2017, the National Academy of Sciences and the National Academy of Medicinetwo leading medical authorities that propose medical and research guidelines for a wide range of research and medical topics issued sweeping recommendations for the use of CRISPR technology. In their joint Human Genome Editing: Science, Ethics, and Governance report, the panel of experts deemed the development of novel treatments and therapies an appropriate use of the technology. The recommendations also approve investigating CRISPR in clinical trials for preventing serious diseases and disabilities and basic laboratory research to further understand the impact of this technology.

The authors of the report caution against human genome editing for purposes other than treatment and prevention of diseases and disabilities. But the line between treatment and enhancement isnt always clear, says Caplan. And policing so-called ethical uses of CRISPR technology will be increasingly difficult because single genes are responsible for a myriad diseases and traits. You don’t realize that you’re changing DNA in places you don’t want to, he says.

A source familiar with the controversial Oregon research reported last week told Newsweek that a major journal will publish a paper on the work by the end of this week. According to The Niche, a blog produced by the Knoepfler Lab at University of California Davis School of Medicine in Sacramento, California, the paper is slated to be published in Nature . Mitalipov did not respond to Newsweek s requests for comment or confirmation.

Caplan hopes that publication of the paper will initiate further discussion about the ethics of experimenting with CRISPR including practical measures such as a registry for scientists conducting studies through private funding. We need to have an international meeting about what are the penalties of doing this, he says. Will you go to jail or get a fine?

This story has been updated to note that the initial report of the CRISPR research in Oregon was based on a leak, but did not necessarily misconstrue the research.

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Gene Editing Is Revolutionizing Medicine but Causing a Government Ethics Nightmare – Newsweek

In US first, scientists edit genes of human embryos – Indiana Gazette

For the first time in the United States, scientists have edited the genes of human embryos, a controversial step toward someday helping babies avoid inherited diseases.

The experiment was just an exercise in science the embryos were not allowed to develop for more than a few days and were never intended to be implanted into a womb, according to MIT Technology Review, which first reported the news.

Officials at Oregon Health & Science University confirmed Thursday that the work took place there and said results would be published in a journal soon. It is thought to be the first such work in the U.S.; previous experiments like this have been reported from China. How many embryos were created and edited in the experiments has not been revealed.

The Oregon scientists reportedly used a technique called CRISPR, which allows specific sections of DNA to be altered or replaced. It’s like using a molecular scissors to cut and paste DNA, and is much more precise than some types of gene therapy that cannot ensure that desired changes will take place exactly where and as intended. With gene editing, these so-called “germline” changes are permanent and would be passed down to any offspring.

The approach holds great potential to avoid many genetic diseases, but has raised fears of “designer babies” if done for less lofty reasons, such as producing desirable traits.

Last year, Britain said some of its scientists could edit embryo genes to better understand human development.

And earlier this year in the U.S., the National Academy of Sciences and National Academy of Medicine said in a report that altering the genes of embryos might be OK if done under strict criteria and aimed at preventing serious disease.

“This is the kind of research that the report discussed,” University of Wisconsin-Madison bioethicist R. Alta Charo said of the news of Oregon’s work. She co-led the National Academies panel but was not commenting on its behalf Thursday.

“This was purely laboratory-based work that is incredibly valuable for helping us understand how one might make these germline changes in a way that is precise and safe. But it’s only a first step,” she said.

“We still have regulatory barriers in the United States to ever trying this to achieve a pregnancy. The public has plenty of time” to weigh in on whether that should occur, she said. “Any such experiment aimed at a pregnancy would need FDA approval, and the agency is currently not allowed to even consider such a request” because of limits set by Congress.

One prominent genetics expert, Dr. Eric Topol, director of the Scripps Translational Science Institute in La Jolla, Calif., said gene editing of embryos is “an unstoppable, inevitable science, and this is more proof it can be done.”

Experiments are in the works now in the U.S. using gene-edited cells to try to treat people with various diseases, but “in order to really have a cure, you want to get this at the embryo stage,” he said. “If it isn’t done in this country, it will be done elsewhere.”

There are other ways that some parents who know they carry a problem gene can avoid passing it to their children, he added. They can create embryos through in vitro fertilization, screen them in the lab and implant only ones free of the defect.

Dr. Robert C. Green, a medical geneticist at Harvard Medical School, said the prospect of editing embryos to avoid disease “is inevitable and exciting,” and that “with proper controls in place, it’s going to lead to huge advances in human health.”

The need for it is clear, he added: “Our research has suggested that there are far more disease-associated mutations in the general public than was previously suspected.”

Hank Greely, director of Stanford University’s Center for Law and the Biosciences, called CRISPR “the most exciting thing I’ve seen in biology in the 25 years I’ve been watching it,” with tremendous possibilities to aid human health.

“Everybody should calm down” because this is just one of many steps advancing the science, and there are regulatory safeguards already in place. “We’ve got time to do it carefully,” he said.

Michael Watson, executive director of the American College of Medical Genetics and Genomics, said the college thinks that any work aimed at pregnancy is premature, but the lab work is a necessary first step.

“That’s the only way we’re going to learn” if it’s safe or feasible, he said.

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In US first, scientists edit genes of human embryos – Indiana Gazette

How precision medicine, immunotherapy are influencing clinical trial design for cancer drugs – MedCity News

Newfound understanding of the biology of cancer has spurred a wave of oncology drug approvals, creating previously unheard of treatment success. At the same time, this degree of success leads to a rapidly shifting competitive landscape, presenting unique challenges for pharma companies planning cancer clinical trials. What steps can the pharma community take to remain flexible and responsive in this new Golden Age of smarter therapies?

An accelerated pace of approvals

Oncology research and improvements in technology have ushered in a new era of more targeted therapeutics based on the mechanisms that drive cancer. Technological advances in tumor imaging and next-generation sequencing have sped the development of precision medicines, treatments that target specific genetic markers rather than relying purely on cytotoxicity. The decreased cost of analysis has led to increased accessibility of genetic data, allowing leading cancer hospitals to use NGS to guide treatment decisions for new cancer patients based on their cancers specific genetic makeup. In addition, the field is seeing tremendous strides in immunotherapy approaches, which seek to activate the immune systemto defeat cancer cells.

In response to the early success of precision medicines and immunotherapies, the U.S. Food and Drug Administration is approving drugs faster and more frequently. In 2014, all but one oncology drug approved by the FDA received some form of expedited designation. By the following year, more oncology drugs were approved by the FDA than ever before.

The rapid pace of new drug approvals has, in turn, increased the pace of changes to the standard of care, now determined as much by biomarkers as by histology. New data continues to shape the current clinical practice guidelines. The National Comprehensive Cancer Network has updated guidelines for lung cancer five times since they were first issued in late 2016.

The impact on pharma

The accelerated pace of drug approvals for cancer has created a flurry of activity in the pharma community. As of 2014, there were nearly 800 cancer drugs in development. and in 2017 more than 12,000 active cancer clinical trials. Looking just at the field of immuno-oncology and checkpoint inhibitors, which have exploded onto the market in recent years, there are over 750 active studies with checkpoint combinations today. Conducting cancer clinical trials has always been complex, but planning successful clinical trials amid a rapidly shifting oncology landscape presents unique challenges for pharma sponsors.

To provide useful results, clinical trials should use the highest standard of approved care for their participants,but the standard of care in oncology is constantly shifting. As treatments target increasingly specific disease states, clinical trial design must evolve to generate enough data from relatively small sample populations. In an increasingly competitive space, pharma sponsors are tasked with finding the quickest ways to gather safety and efficacy data that satisfies FDA requirements.

Now more than ever, the pharma community must become flexible and responsive to a rapidly changing marketplace. Although sponsors can attempt to anticipate future treatment approvals and incorporate them into statistical models, there is a limit to how far into the future they are able to forecast. Sponsors may, therefore, wish to consider the following ways to design their clinical trial protocols with a degree of adaptability to have the greatest chance of success.

Adjust inclusion/exclusion criteria

In order to recruit patients more quickly, sponsors can adjust the inclusion/exclusion criteria to be less strict. However, this approach may yield a heterogeneous population, which might have an undesired effect on data quality and statistical efficacy.

Allow investigators choice

For trials that combine or compare an investigational drug with the existing standard of care that is likely to change, sponsors may need to consider letting investigators choose from a menu of comparators. The statistical and logistic implications, as well as the timeline, are important to consider.

Plan for critical amendments

Portions of a clinical trial can be completed before a new therapy is generally available or reimbursed. Although making changes to the protocol during the course of a clinical study are generally not desired because of added time and cost, there are certain cases where making critical amendments is necessary.

If first-line approval for a drug is already being pursued, sponsors can take advantage of a gap in therapeutic options by adding another arm to their trials that demonstrateeffectiveness as a second-line therapy.

Use innovative trial designs

Changes to protocol designs are also influencing how quickly enough evidence can be generated for the FDA to grant approval. Two innovative new designs are basket trials and umbrella trials. In a basket trial, patients are recruited based on the genetic makeup of their tumor rather than tumor histology. The recent FDA approval of pembrolizumab was the first approval based on a common biomarker rather than the location in the body where the tumor originated. Umbrella trials allow researchers to test multiple indications and combinations for a given therapy, with the potential to spin any arm off as its own registrational component.

Its an exciting time to be in cancer research and to watch some of these therapies move rapidly from clinic to improving the lives of patients. Sponsors play an important role during development by spearheading innovation, staying flexible, and planning accordingly for the rapid pace.

Photo: DrAfter123, Getty Images

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How precision medicine, immunotherapy are influencing clinical trial design for cancer drugs – MedCity News

For Indian doctors, it’s written in the genes not stars – Economic Times

BENGALURU: When five-year-old Chathura Corea from Sri Lanka landed in India for cancer treatment, his physician Sachin Jadhav got a genetic test done on his blood sample before starting any kind of treatment. Corea had been diagnosed with a very rare form of blood cancer called Juvenile Myelomonocytic Leukaemia (JMML). After a genetic test, Jadhav concluded that a simple chemotherapy would not suffice and the kid needs a bone-marrow transplant”.

The (genetic) test helped me identify what line of treatment to give providing maximising the chance of cure and in planning treatment better, says Jadhav, who has partnered with Bengaluru-based MedGenome Labs which provides genetic tests for a range of ailments like cancer, metabolic diseases, eye diseases, neurological and prenatal disorders.

Increasingly , doctors like Jadhav are asking patients to take genetic tests to identify ‘faulty’ genes in treating genetic diseases better.

MedGenome has seen the number of samples triple for genetic tests in of samples triple for genetic tests in the last one year.

We now get about 600-800 samples a month, said VL Ramprasad, COO of MedGenome Labs. The uptake is primarily due to increased awareness among clinicians in India who see a scope for better results and efficient treatment, he said.

Another lab, Stand Life Sciences has also seen a similar spike in the number of samples received.Strand has seen a 250% growth in the number of samples last year, and we have done about 5,000 samples this year, said cofounder Vijay Chandru. The science behind these tests is straight forward: everything about us -the length of our hair, the colour of our eyes, the complexion of our skin is coded onto the DNA -which also has hidden hints of the possible disease one might get. Scientists analyse the genetic code and figure out what mutation causes a specific disease. As the awareness among doctors increases, revenues have been surging. MedGenome revenues have doubled every year. The lab’s revenues have grown from $4 million in 2015 to $16.5 million in 2017.

At this point, we are just scratching the surface, says Chandru of Strand life sciences, adding, The addressable market is 500,000 people according to India Council of Medical Research (ICMR) report. Say , 20% people can afford the tests… 100,000 peo ple could be tested. Right now, only 5,000 people are being tested.

These genetic tests cost about Rs 30,000- 40,000 for a single test. Only 2% of Indian population is covered by insurance. Hence, affordability is another bottleneck in the widespread adoption of genetic tests, said Chirantan Bose, VP of Clinical services at Medgenome.

Aside from providing insights to clinicians for better diagnosis, the milestone for genetic tests is `targeted therapy’ for specific diseases. For instance, precision medicine in the treatment of cancer when the drug hits only the cancer cells and not the entire body (like in chemotherapy). Genetic testing paves way for precision medicine. Consumers too want to dig into their genes to know more about their family history , lifestyle tendencies and information about their ancestry .

Mapmygenome provides a report on 100 different conditions including inherited and acquired genetic health risks. The firm’s product, Genomepatri, has found massive traction and the number of samples have tripled over the samples we received last year, says Anu Acharya, cofounder of Mapmygenome, adding that demand was not just coming from metros but even from tier-II towns across India.

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For Indian doctors, it’s written in the genes not stars – Economic Times

CRISPR Pioneer Zhang Preaches Extra Caution In Human Gene Editing – Xconomy

Xconomy Boston

A leading genome-editing researcher is urging extra caution as drug companies race to turn the landmark technology he helped create into human medicine.

In a paper published today in Nature Medicine, Feng Zhang of the Broad Institute of MIT and Harvard and colleague David Scott argue that researchers should analyze the DNA of patients before giving them experimental medicines that alter their genes with the breakthrough technology CRISPR. The suggestion, among others in the paper, stems from a deeper look at the wide array of subtle differences in human DNA.

Zhang is a key inventor of CRISPR-Cas9, which describes a two-part biological system that slips into the nucleus of cells and irreversibly alters DNA. One part is an enzyme, natures molecular scissors, which cuts DNA. The second part is a string of ribonucleic acid (RNA) that guides the enzyme to the proper spot. In five years since its invention, CRISPR-Cas9 has become a mainstay of biological research, and researchers including Zhang (pictured above) have moved quickly to improve upon its components. His work is at the center of a long-running patent battle to determine ownership of the technology.

Zhang and Scotts recommendation taps into a long-running debate in the gene-editing field about off-target effectsthe fear of misplaced cuts causing unintended harm. Most recently, the FDA took up a similar issue at a meeting to assess a type of cell therapy, known as CAR-T, for kids with leukemia. The FDA highlighted the risk that the cells, which have certain genes edited to make them better cancer fighters, may cause secondary cancers long after a patients leukemia has been cured. (FDA advisors unanimously endorsed the therapys approval nonetheless.)

Some researchers say there should be near certainty that gene altering techniques wont go awry before testing in humans, caution that stems in part from gene therapy experiments in the U.S. and Europe nearly 20 years ago that killed an American teenager and triggered leukemia in several European boys.

While no medicine is risk-free, other researchers say the tools to gauge risk have improved.

Andy May, senior director of genome engineering at the Chan Zuckerberg Biohub in San Francisco, calls Zhang and Scotts recommendation for patient prescreening a good discussion point, but the danger is someone will pick up on this and say you cant push forward [with a CRISPR drug] until everyone is sequenced.

Its an extremely conservative path to take, says May, who until recently was the chief scientific officer at Caribou Biosciences, a Berkeley, CA-based firm in charge of turning the discoveries of UC Berkeleys Jennifer Doudna and her colleagues into commercial technology. (May was also a board member of Cambridge, MA-based Intellia Therapeutics (NASDAQ: NTLA), which has exclusive license to use Caribous technology in human therapeutics.)

Berkeley is leading the challenge to Zhangs CRISPR patents and last week filed the first details in its appeal of a recent court decision in favor of Zhang and the Broad Institute.

Zhang sees prescreening as a form of companion diagnostic, which drug companies frequently use to identify the right patients for a study. A whole genome sequencewhich costs about $1,000could filter out patients unlikely to benefit from a treatment or at higher risk of unintended consequences, such as cancer. In the long run, it could also encourage developers to create more variations of a treatment to make genome-editing based therapeutics as broadly available as possible, said Zhang.

Its well known that human genetic variation is a hurdle in the quest to treat genetic diseases either by knocking out disease-causing genes or replacing them with healthy versions. But Zhang and Scott use newly available genetic information to deepen that understanding. In one Broad Institute database with genetic information from more than 60,000 people, they find one genetic variation for every eight letters, or nucleotides, in the exomethat is, the sections of DNA that contain instructions to make proteins. (There are 6 billion nucleotides in each of our cells.) The wide menu of differences is, in effect, an open door to misplaced cuts that CRISPRs enzymes might be prone to.

Zhang and others are working on many kinds of enzymes, from variations on the workhorse Cas9, to new ones entirely. He and Scott found that the deep pool of genetic variation makes some forms of the Cas enzyme more likely than others to go awry, depending on the three-nucleotide sequence they lock onto in the targeted DNA.

Zhang and Scott write that CRISPR drug developers should avoid trying to edit DNA strings that are likely to have high variation. In their paper, they examine 12 disease-causing genes. While more common diseases, such as those related to high cholesterol, will contain higher genetic variation because of the broader affected population, every gene, common or not, contains regions of high and low variation. Zhang and Scott say developers can build strategies around the gene regions they are targeting.

For example, going after a more common disease might require a wider variety of product candidates, akin to a plumber bringing an extra-large set of wrenches, with finer gradations between each wrench, to a job site with an unpredictable range of pipe sizes.

CRISPR companies say they are doing just that. We have always made specificity a fundamental part of our program, says Editas Medicine CEO Katrine Bosley. Zhang is a founder of Editas (NASDAQ: EDIT), which has exclusive license to the Broads Next Page

Alex Lash is Xconomy’s National Biotech Editor. He is based in San Francisco.

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CRISPR Pioneer Zhang Preaches Extra Caution In Human Gene Editing – Xconomy

Understanding Williams Syndrome: Genetic condition brings host of medical problems but also unlimited capacity to love – WGN-TV

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How a heart that is broken physically works flawlessly when it comes to emotion. For children born with Williams Syndrome, compromised heart function opens the door for an unlimited capacity to love.

Maya is a happy, playful 18-month-old.

The moment I get home from work, the moment she wakes up, she’s usually always smiling and happy, says Mayas father Scott Ottenheimer. We celebrate and get so excited aboutthe milestones because they mean so much to us.

When Maya was born inFebruary 2016, she hada heart murmur.

Mayas mother Jenna Ottenheimer says, In her case, the heart murmur ended up being a serious defect. She was born with narrowing of both her aorta and pulmonary arteries. It was absolutely devastating. It was the darkest time of my life.

It was the first indication of their newborn’s complex medical condition.And as Scott and Jenna braced for their daughter’s open heart surgery, the first of several procedures, they learned of Maya’sdiagnosis — Williams Syndrome.

People say, ‘What’s Williams syndrome?’ And I say, I’ve never heard of it either before Maya, Scott says.

Children or adults with Williams Syndrome can experience a whole host of medical problems, says Dr Darrel Waggoner, medical geneticist at the University of Chicago Medicine. They can experience problems related to growth, development, eating.

Williams Syndrome is a genetic condition that affects one in 10,000 people worldwide.

Dr Waggoner says it stems from a chromosome abnormality.

This is a picture of chromosome 7. This white band that’s the piece of genetic code thats missing or deleted, says Dr Waggoner. If you think of your genetic code as a set of instructions on how to grow a heart and develop your brain, if you are missing some of those instructions then it leads to changes.

Jenna explains, Maya has a couple other medical problems we follow. We see gastroenterology for acid reflux. Her kidneys are affected.

Along with regular monitoring of hermedical issues, Mayareceives severalhours a week of physical, occupational and speech therapy.

I’m very proud of her andhow far she’s come in 18 months, Jenna says. She’s crawling and pulling to stand and we feel confident she’s going to walk soon. She will talk one day. It’s just with Williams Syndrome the delays can be life long.

Amanda and Andrew McDaniel understand completely.

Like Maya, their son Tom was born with a major heart defect.

Were very proud, says Andrew. Weve worked very hard to bring him along.

Amandas pregnancy was uneventful, but as soon as her son was born, he was rushed to the neonatal intensive care unit. And within days it was confirmed he had Williams Syndrome along with another condition that caused problems with his legs and spine.

It was a lot to digest, a lot to take in, Amanda says. We were told to expect a kid who wouldnt sleep, didnt want to eat and would have extreme colic.

Connecting with other families like the Ottenheimers through the Williams Syndrome Association has helped the McDaniels navigate their sons health challenges.

Amanda says, Our biggest struggle in the next months was all the follow up appointments. We saw 12 different specialists because its such a spectrum disorder. Hes had countless tests and procedures.

Now at 2-years-old, Tom is working hard to gain more mobility. Therapy is a constant. But he takes it all in stride. Amid all the challenges, Maya and Tom smile. Its the special gift of people with Williams Syndrome.

Once his personality came in he was always sweet and charming, Andrew says. As hard as it was, that made it worth it.

Dr Waggoner explains, Behaviorally, the children some of them have a characteristic personality. They are very friendly, very social.

He wants the entire restaurant when we go out to dinner to interact with him. He cant walk and he cant talk, but he gets every adult in the restaurant to come up and interact with him, says Amanda. But there is so much more. I want him to be accepted. I want him to have friends.

What she has taught me is how can we say that it’s a disorder to be so friendly and so happy? Jenna says. I think kids and adults with Williams Syndrome can teach us a lot about accepting others and being friendly and happy and open minded and open hearted, because kids with Williams Syndrome are genetically born that way.

The joy their children bring is infectious. But the parents WGN spoke with want others to know there is so much more to learn about Williams Syndrome. Thats why they shared their stories to raise awareness and foster a better understanding of some of the major struggles they face.

You can learn more at https://williams-syndrome.org/

Email info@williams-syndrome.org

Williams Syndrome Association: 248-244-2229

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Understanding Williams Syndrome: Genetic condition brings host of medical problems but also unlimited capacity to love – WGN-TV

In US first, scientists edit genes of human embryos – ABC News

For the first time in the United States, scientists have edited the genes of human embryos, a controversial step toward someday helping babies avoid inherited diseases.

The experiment was just an exercise in science the embryos were not allowed to develop for more than a few days and were never intended to be implanted into a womb, according to MIT Technology Review, which first reported the news.

Officials at Oregon Health & Science University confirmed Thursday that the work took place there and said results would be published in a journal soon. It is thought to be the first such work in the U.S.; previous experiments like this have been reported from China. How many embryos were created and edited in the experiments has not been revealed.

The Oregon scientists reportedly used a technique called CRISPR, which allows specific sections of DNA to be altered or replaced. It’s like using a molecular scissors to cut and paste DNA, and is much more precise than some types of gene therapy that cannot ensure that desired changes will take place exactly where and as intended. With gene editing, these so-called “germline” changes are permanent and would be passed down to any offspring.

The approach holds great potential to avoid many genetic diseases, but has raised fears of “designer babies” if done for less lofty reasons, such as producing desirable traits.

Last year, Britain said some of its scientists could edit embryo genes to better understand human development.

And earlier this year in the U.S., the National Academy of Sciences and National Academy of Medicine said in a report that altering the genes of embryos might be OK if done under strict criteria and aimed at preventing serious disease.

“This is the kind of research that the report discussed,” University of Wisconsin-Madison bioethicist R. Alta Charo said of the news of Oregon’s work. She co-led the National Academies panel but was not commenting on its behalf Thursday.

“This was purely laboratory-based work that is incredibly valuable for helping us understand how one might make these germline changes in a way that is precise and safe. But it’s only a first step,” she said.

“We still have regulatory barriers in the United States to ever trying this to achieve a pregnancy. The public has plenty of time” to weigh in on whether that should occur, she said. “Any such experiment aimed at a pregnancy would need FDA approval, and the agency is currently not allowed to even consider such a request” because of limits set by Congress.

One prominent genetics expert, Dr. Eric Topol, director of the Scripps Translational Science Institute in La Jolla, California, said gene editing of embryos is “an unstoppable, inevitable science, and this is more proof it can be done.”

Experiments are in the works now in the U.S. using gene-edited cells to try to treat people with various diseases, but “in order to really have a cure, you want to get this at the embryo stage,” he said. “If it isn’t done in this country, it will be done elsewhere.”

There are other ways that some parents who know they carry a problem gene can avoid passing it to their children, he added. They can create embryos through in vitro fertilization, screen them in the lab and implant only ones free of the defect.

Dr. Robert C. Green, a medical geneticist at Harvard Medical School, said the prospect of editing embryos to avoid disease “is inevitable and exciting,” and that “with proper controls in place, it’s going to lead to huge advances in human health.”

The need for it is clear, he added: “Our research has suggested that there are far more disease-associated mutations in the general public than was previously suspected.”

Hank Greely, director of Stanford University’s Center for Law and the Biosciences, called CRISPR “the most exciting thing I’ve seen in biology in the 25 years I’ve been watching it,” with tremendous possibilities to aid human health.

“Everybody should calm down” because this is just one of many steps advancing the science, and there are regulatory safeguards already in place. “We’ve got time to do it carefully,” he said.

Michael Watson, executive director of the American College of Medical Genetics and Genomics, said the college thinks that any work aimed at pregnancy is premature, but the lab work is a necessary first step.

“That’s the only way we’re going to learn” if it’s safe or feasible, he said.

Marilynn Marchione can be followed at http://twitter.com/MMarchioneAP

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In US first, scientists edit genes of human embryos – ABC News

Stanford Center for Definitive and Curative Medicine to tackle genetic diseases – Scope (blog)

Good news for people suffering from genetic diseases and for those who could be helped with stem cell therapies. This week, Stanford announced the creation of the Center for Definitive and Curative Medicine, a new center that aims to bring life-changing advances to millions of patients.

The Center for Definitive and Curative Medicine is going to be a major force in theprecision healthrevolution, saidLloyd Minor, MD, dean of the School of Medicine, in a press release. Our hope is that stem cell and gene-based therapeutics will enable Stanford Medicine to not just manage illness but cure it decisively and keep people healthy over a lifetime.

The center plans to tap the rich vein of stem cell and gene therapy research underway at Stanford. These techniques pinpoint problems causing disease and introduce functional copies of genes or cells to replace malfunctioning ones. Its exciting work with the potential to make real changes in patient lives and Stanford with its deep strengths in research and clinical care is poised to lead.

The release explains:

Housed within theDepartment of Pediatrics, the new center will be directed by renowned clinician and scientistMaria Grazia Roncarolo, MD, the George D. Smith Professor in Stem Cell and Regenerative Medicine, and professor of pediatrics and of medicine.

It is a privilege to lead the center and to leverage my previous experience to build Stanfords preeminence in stem cell and gene therapies, said Roncarolo, who is also chief of pediatric stem cell transplantation and regenerative medicine, co-director of theBass Center for Childhood Cancer and Blood Diseasesand co-director of theStanford Institute for Stem Cell Biology and Regenerative Medicine. Stanford Medicines unique environment brings together scientific discovery, translational medicine and clinical treatment. We will accelerate Stanfords fundamental discoveries toward novel stem cell and gene therapies to transform the field and to bring cures to hundreds of diseases affecting millions of children worldwide.

Previously: Stanford scientists describe stem-cell and gene-therapy advances in scientific symposium Photo of Maria Grazia Roncarolo by Norbert von der Groeben

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Stanford Center for Definitive and Curative Medicine to tackle genetic diseases – Scope (blog)

Scientists identify gene variations that determine lifespan – Medical News Today

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Scientists identify gene variations that determine lifespan – Medical News Today

Sorry, it’s all in your genes – Daily Trust

Enough of blaming your environment every time you come down with an illness. Heres a new possibility: it could all be in your genes.

And proponents of genetic medicine are pushing the practice a notch higher in Nigeria.

The premise is that specific genes are responsible for specific conditions, and finding the right gene is the silver bullet.

Genetic disorder in medicine is not very well recognised, says Hyung Goo Kim, associate professor in neuroscience and regenerative medicine department at Augusta University, USA.

Hes part of a team expanding the scope of regenerative medicine through lectures at the National Hospital, Abuja.

Many people suffer disease but the [cause] is not recognised. The point is to find the disease gene for diagnosis and in the long run cure and treatment.

If we can identify the gene causing the disorder then we can understand the biology of the disorder more than before. That way we can intervene to try to cure and treat.

Regenerative medicine works by allowing body tissues to reprogramme themselves to act in different ways depending on what they are required to do or where they are placed.

For this, researchers use pluripotent cells, capable of becoming just about anything, and abundant in bone marrow.

Every disease in your body system can actually be tackled if we engineer the production of stem cells to fight that disease, says Prosper Igboeli, a professor at University of Nigeria and Augusta University.

The science of regeneration makes it possible to induce pluripotent stem cells.

Igboeli cautiously explains it is like taking skin and reorganising it to make any cell, even sperm.

I dont like to say things that are not correct. But we are having this new feeling that we can take your skin and make sperm out of it.

The bone marrow is a reserve of cells that can be re-engineered and configured through passage, injected into organs and organs respond to that particular disease state and revert back to normal.

The payoff is in having your body produce what you need for a cure instead of popping pills.

The range is anything from infertility and diabetes to spinal cord injuries and cancer.

Some endeavours have reached clinical stage, including experimental treatment for premature ovarian failure and polycystic ovarian syndrome.

National Hospital is building up its interest in stem cell research and looking at bone marrow transplantation as a possibility.

Health care research provides answers to questions lingering in the minds of health care providers in terms of diseases they are trying to manage, says Dr Jafar Momoh, chief medical director of the hospital.

The first world spends a lot of money on research and National Hospital is trying to collaborate with various [nongovernmental organisations] to deliver on the mandate for research.

We are looking at bone marrow transplantation. This is something the country needs for various diseases.

Research here will bring in funding from donor agencies interested in new research areas. Hence we need a robust research program. We have published papers but we want to take it to another level: molecular genetics, stem cell medicine and bone marrow transplantation, said Momoh.

Genetic medicine research is big in Egypt and Tunisia.

The effort now is to build a network of experts and a network to accumulate a database to help identify disease genes.

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Sorry, it’s all in your genes – Daily Trust

Big Data Shows Big Promise in Medicine – Bloomberg

A tumor is a trove of data.

In handling some kinds of life-or-death medical judgments, computers have already have surpassed the abilities of doctors. Were looking at something like promise of self-driving cars, according to Zak Kohane, a doctor and researcher at Harvard Medical School. On the roads, replacing drivers with computers could save thousands of lives that would otherwise be lost to human error. In medicine, replacing intuition with machine intelligence might save patients from deadly drug side effects or otherwise incurable cancers.

Consider precision medicine, which involvestailoring drugs to individual patients. And to understand its promise, look toShirley Pepke, a physicist by training who migratedinto computational biology. When she developed a deadly cancer, she responded like a scientist and fought it using big data. And she is winning. She shared her story at a recent conference organized by Kohane.

In 2013, Pepke was diagnosed with advanced ovarian cancer. She was 46, andher kids were 9 and 3. It was just two months after her annual gynecological exam. She had symptoms, which the doctors brushed off, until her bloating got so bad she insisted on an ultrasound. She was carrying six liters of fluid caused by the cancer, which had metastasized. Her doctor, she remembers, said, I guess you werent making this up.

She did what most people do in her position. She agreed to a course of chemotherapy that doctors thought would extend her life and offered a very slim chance of curing her. It was a harsh mixture pumped directly into her abdomen.

She also did something most people wouldnt know how to do — she started looking for useful data. After all, tumors are full of data. They carry DNA with various abnormalities, some of which make them malignant or resistant to certain drugs. Armed with that information, doctors design more effective, individualized treatments. Already, breast cancers are treated differently depending on whether they have a mutation in a gene called HER2. So far, scientists have found no such genetic divisions for ovarian cancers.

But there was some data. Years earlier, scientistshad started a data bank called the Cancer Genome Atlas. There were genetic sequences on about 400 ovarian tumors. To help her extract useful information from the data, she turned to Greg ver Steeg, a professor at the University of Southern California, who was working on an automated pattern-recognition technique called correlation explanation, or CorEx. It had not been used to evaluate cancer, but she and ver Steeg thought it might work.She also got genetic sequencing done on her tumor.

In the meantime, she found out she was not one of the lucky patients cured by chemotherapy. The cancer came back after a short remission. A doctor told her that she would only feel worse every day for the short remainder of her life.

But CorEx had turned up a clue. Her tumor had something on common with those of the luckier women who responded to the chemotherapy — an off-the-charts signal for an immune system product called cytokines. She reasoned that in those luckier patients, the immune system was helping kill the cancer, but in her case, there was something blocking it.

Eventually she concluded that her one shot at survival would be to take a drug called a checkpoint inhibitor, which is geared to break down cancer cells defenses against the immune system.

Checkpoint inhibitors are only approved so far for melanoma. Doctors can still prescribe such drugs for other uses, though insurance companies wont necessarily cover them. She ended up paying thousands of dollars out of pocket. At the same time, she went in for another round of chemotherapy. The checkpoint inhibitor destroyed her thyroid gland, she said, and the chemotherapy was damaging her kidneys. She stopped, not knowing whether her cancer was still there or not. To the surprise of her doctors, she started to get better. Her cancer became undetectable. Still healthy today, she works on ways to allow other cancer patients to benefit from big data the way she did.

Kohane, the Harvard Medical School researcher, said similar data-driven efforts might help find side effects of approved drugs. Clinical trials are often not big enough or long-running enough to pick up even deadly side effects that show up when a drug is released to millions of people. Thousands died from heart attacks associated with the painkiller Vioxx before it was taken off the market.

Last month, an analysis by another health site suggested a connection between the rheumatoid arthritis drug Actemra and heart attack deaths, though the drug had been sold to doctors and their patients without warning of any added risk of death. Kohane suspects there could be many other unnecessary deaths from drugs whose side effects didnt show up in testing.

So whats holding this technology back? Others are putting big money into big data with the aim of selling us things and influencing our votes. Why not use it to save lives?

First theres the barrier of tradition, said Kohane, whose academic specialty is bioinformatics, a combination of math, medicine and computer science. Medicine does not understand itself as an information-processing discipline, he said. It still sees itself as a combination of intuitive leaps and hard science. And doctors arent collecting the right kinds of data. Were investing in information technology thats not optimized to do anything medically interesting, he said. Its there to maximize income but not to make us better doctors.

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Physicians arent likely to be replaced by algorithms, at least not right away, but their skill sets might have to change. Already, machines have proven themselves better than humans in the ability to read scans and evaluate skin lesions. Pepke ended her talk by saying that in the future, doctors may have to think less statistically and more scientifically. Her doctors made decisions based on rote statistical information about what would benefit the average patient — but Shirley Pepke was not the average patient. The status quo is an advance over guessing or tradition, but medicine has the potential to do so much better.

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

To contact the author of this story: Faye Flam at fflam1@bloomberg.net

To contact the editor responsible for this story: Tracy Walsh at twalsh67@bloomberg.net

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Big Data Shows Big Promise in Medicine – Bloomberg

The 16 genetic markers that can cut a life story short – Medical Xpress

July 27, 2017 Credit: CC0 Public Domain

The answer to how long each of us will live is partly encoded in our genome. Researchers have identified 16 genetic markers associated with a decreased lifespan, including 14 new to science. This is the largest set of markers of lifespan uncovered to date. About 10 percent of the population carries some configurations of these markers that shorten their life by over a year compared with the population average. Spearheaded by scientists from the SIB Swiss Institute of Bioinformatics, the Lausanne University Hospital (CHUV), the University of Lausanne and the EPFL, the study provides a powerful computational framework to uncover the genetics of our time of death, and ultimately of any disease. The study is published today in Nature Communications.

Why do some of us live longer than others? While the environment in which we live including our socio-economic status or the food we eat plays the biggest part, about 20 to 30 percent of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity.

“Until now, the most comprehensive studies had found only two hits in the genome,” points out Prof. Zoltn Kutalik, Group Leader at SIB and assistant professor at the Institute of Social and Preventive Medicine (CHUV).

In a new study, a team of scientists, led by Kutalik, has used an innovative computational approach to analyse a dataset of 116,279 individuals and probe 2.3 million human SNPs.

An unparalleled number of SNPs associated with lifespan (16) were uncovered, including 14 new to science. “In our approach, we prioritized changes in the DNA known to be linked to age-related diseases in order to scan the genome more efficiently,” says Kutalik. “This is the largest set of lifespan-associated genetic markers ever uncovered.”

About 1 in 10 people carry some configurations of these markers that shorten their life by over a year compared with the population average. In addition, a person inheriting a lifespan-shortening version of one of these SNPs may die up to seven months earlier.

The approach also enabled the researchers to explore how the DNA changes affected lifespan in a holistic way. They found that most SNPs had an effect on lifespan by impacting more than a single disease or risk factor, for example through being more addicted to smoking as well as through being predisposed to schizophrenia.

The discovered SNPs, combined with gene expression data, allowed the researchers to identify that lower brain expression of three genes neighbouring the SNPs (RBM6, SULT1A1 and CHRNA5, involved in nicotine dependence) was causally linked to increased lifespan.

These three genes could therefore act as biomarkers of longevity, i.e. survival beyond 85-100 years. “To support this hypothesis, we have shown that mice with a lower brain expression level of RBM6 lived substantially longer,” comments Prof. Johan Auwerx, professor at the EPFL.

“Interestingly, the gene expression impact of some of these SNPs in humans is analogous to the consequence of a low-calorie diet in mice, which is known to have positive effects on lifespan,” adds Prof. Marc Robinson-Rechavi, SIB Group Leader and professor at the University of Lausanne.

“Our findings reveal shared molecular mechanisms between human and model organisms, which will be explored in more depth in the future,” concludes Prof. Bart Deplancke, SIB Group Leader and professor at the EPFL.

This study, which is a part of the AgingX Project supported by SystemsX.ch (the Swiss Initiative in Systems Biology), therefore brings us a step closer to grasping the mechanisms of human aging and longevity. It also proposes an innovative computational framework to improve the power of genomewide investigations of diseases more generally. As such, the framework could have promising applications in the field of personalized medicine.

Explore further: Study shows smoking doesn’t always mean a shortened life span or cancer

More information: Aaron F. McDaid et al. Bayesian association scan reveals loci associated with human lifespan and linked biomarkers, Nature Communications (2017). DOI: 10.1038/NCOMMS15842

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The 16 genetic markers that can cut a life story short – Medical Xpress

First Editing of Human Embryos Performed in United States – NBCNews.com

Human embryos on a petri dish are viewed through a microscope. Sandy Huffaker / Bloomberg via Getty Images file

Some countries have signed a convention prohibiting the practice on concerns it could be used to create so-called designer babies.

Results of the peer-reviewed study are expected to be published soon in a scientific journal, according to OHSU spokesman Eric Robinson.

The research, led by Shoukhrat Mitalipov, head of OHSU’s Center for Embryonic Cell and Gene Therapy, involves a technology known as CRISPR that has opened up new frontiers in genetic medicine because of its ability to modify genes quickly and efficiently.

CRISPR works as a type of molecular scissors that can selectively trim away unwanted parts of the genome, and replace it with new stretches of DNA.

Scientists in China have published similar studies with mixed results.

In December 2015, scientists and ethicists at an international meeting held at the National Academy of Sciences (NAS) in Washington said it would be “irresponsible” to use gene editing technology in human embryos for therapeutic purposes, such as to correct genetic diseases, until safety and efficacy issues are resolved.

But earlier this year, NAS and the National Academy of Medicine said scientific advances make gene editing in human reproductive cells “a realistic possibility that deserves serious consideration.

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First Editing of Human Embryos Performed in United States – NBCNews.com

Medicine’s Movable Feast: What Jumping Genes Can Teach Us about Treating Disease – Scientific American

When the groundbreaking geneticist Barbara McClintock was born in Hartford, Connecticut, in 1902, her parents initially named her Eleanor. But they soon felt that the name was too delicate for their daughter and began to call her Barbara instead, which they thought better suited her strong personality. Her parents accurately predicted her determination.

To say that McClintock was a pioneer is an understatement. In 1944, she became the third woman to be elected to the US National Academy of Sciences and the first woman to lead the Genetics Society of America. Shortly afterwards, she discovered that certain genetic regions in maize could jump around the chromosome and, consequently, influence the color of mottled ears of maize with kernels ranging from golden yellow to dark purple. She dubbed these jumping bits of genetic code controlling units, which later became known as transposons or transposable elements. Unfortunately, by the mid-1950s, McClintock began to sense that the scientific mainstream was not ready to accept her idea, and she stopped publishing her research into this area to avoid alienation from the scientific establishment. But scientific ideas can re-emerge and integrate into the mainstream, and 30 years later, McClintock received a Nobel Prize in Physiology or Medicine for her revolutionary insights into these moving chunks of genetic code.

In recent years, medical research has uncovered new evidence showing that moving parts of the genome in humans can contribute to life-threatening diseases ranging from cancer to diabetes. For example, a handful of hemophilia cases have been traced to transposable elements that, at some point before the patient was born, or even, perhaps, conceived, inserted themselves into and disrupted genes that facilitate blood clotting. At the same time, experiments also offer mounting data to suggest that some transposable elementsand the genes that these roving bits of DNA help to resurrecthave beneficial roles.

The study of transposable elements is a hotbed of research, according to Josh Meyer, a postdoctoral fellow who studies these bits of DNA at Oregon Health & Science University in Portland. Way back in the mists of time for the field, the general category of these things was junk DNA, he explains. Now, he says, researchers have begun to understand that transposable elements aren’t always neutral genetic components: There’s nothing that transposon biologists love more than to have the discussion of whether these things are, on balance, bad for us or good for us.

Since McClintock’s breakthrough, researchers have identified different classes of transposable elements in the genomes of every organism in which they have sought them, ranging from fruit flies to polar bears. About 3% of the human genome consists of transposons of DNA origin, which belong to the same class as the ones that McClintock studied in maize. The other type of transposable elements, known as retrotransposons, are more abundant in our genome. These include the transposable elements that originate from viruses and make up as much as 10% of the human genome1. These elements typically trace back many millennia. They arise when viruses integrate into the genome of sperm or egg cells, and thus get passed down from one generation to the next.

The ancient viruses that became ‘fossilized’ in the genome remain dormant for the most part, and degenerate over time. However, there are hints that they might have the ability to re-emerge and contribute to illnesses that some scientists say could include autoimmune disease and schizophrenia2. In one example, a 2015 study found elevated levels of one embedded virus, known as human endogenous retrovirus K, in the brains of individuals with amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease3. However, researchers stress that the data do not yet establish a causal link.

Yet another category of retrotransposons, called long interspersed nuclear elements-1, or LINE-1 for short, make up a whopping 17% or more of the human genome4. When LINE-1 retrotransposons move within the genome of reproductive cells and insert themselves in new places, they can disrupt important genes. Researchers have so far identified more than 120 LINE-1 gene insertions, resulting in diseases ranging from muscular dystrophy to cystic fibrosis5.

Much of the focus on transposable elementsand particularly, on endogenous retroviruses and LINE-1shas centered on the possible negative repercussions of these DNA insertions. But work tracing back to the 1980s has suggested that endogenous retroviruses may also support reproductive function in some way6. In 2000, scientists found that remnants of an ancient virus in the human genome encode a protein called syncytin, which cell experiments indicate is important for placental development7. And although it is not shown definitely, there are also hints that an endogenous retrovirus that became embedded in the DNA of a primate ancestor might help boost the production of the digestive enzyme amylase, which helps to break down starch, in our saliva8, 9.

To peer deeper into the effects of transposable elements in humans, geneticist Nels Elde and his colleagues at the University of Utah in Salt Lake City used CRISPRCas9 gene editing to target an endogenous retrovirus called MER41, thought to come from a virus that integrated into the genome perhaps as far back as 60 million years ago. The scientists removed the MER41 element from human cells cultured in a dish. In humans, MER41 appears near genes involved in responding to interferon, a signaling molecule that helps our immune response against pathogens. Notably, as compared with normal cells, cells engineered to lack MER41 were more susceptible to infection by the vaccinia virus, used to inoculate people against smallpox. The findings, reported last year, suggest that MER41 has a crucial role in triggering cells to launch an immune response against pathogens through the interferon pathway10.

Meyer stresses that these insights elevate the already eminent discoveries by McClintock. I would hope she would be extremely gratified and vindicated, he says. She recognized a type of sort of factor of genomic dynamism that no one else had seen before. And I am firmly convinced that it’s going to only become more and more and more central to our understanding of how genomics works.

In 2005, with a freshly minted doctorate in molecular genetics, Nels Elde landed a job as a research fellow in Seattle and was tasked with studying the evolution of the immune system of gibbons, a type of ape. Each morning as he biked to the lab downtown, he would pass the city’s zoo and hear its gibbons calling to each other. Occasionally, he would visit the zoo and look at them, but he had no idea at the time that the squirrel monkeys that he also saw there would feature so largely in his future research. At work, Elde’s primate investigations focused on the gibbon DNA that he was responsible for extracting and analyzing using sequencing machinery.

Then, six years ago, Elde received his first lab of his own to run, at the University of Utah. He did not expect his team’s first discovery there to come so swiftly, or that it would involve transposable elements. Elde had arrived at the university with the intention of learning how cells recognize and defeat invading viruses, such as HIV. But he hadn’t yet obtained the equipment that he needed to run experiments, despite already having two employees who were eager to do work, including his lab manager, Diane Downhour. Given the lack of lab tools, the two lab staff members spent their time on their computers, poking around databases for interesting patterns in DNA. After just two weeks of this, Downhour came into Elde’s office and told him that they had found a couple of extra copies of a particular gene in New World monkeysspecifically, in squirrel monkeys.

Elde initially brushed off Downhour’s insight. I said, ‘Why don’t you go back to the lab and not worry about it?’ he recalls. But a couple of days later, she returned to his office with the idea. I was just in the sort of panicked mode of opening a lab, ordering freezers, trying to set up equipment and hiring people, Elde explains. Diane definitely had to come back and say, ‘Come on, wake up here. Pay attention.’

The gene that they detected multiple copies of in squirrel monkeys is called charged multivesicular body protein 3, or CHMP3. Each squirrel monkey seems to have three variants of the gene. By comparison, humans have only the one, original variant of CHMP3. The gene is thought to exist in multiple versions in the squirrel monkey genome thanks to transposable elements. At some point around 35 million years ago, in an ancestor of the squirrel monkey, LINE-1 retrotransposons are thought to have hopped out of the genome inside the cell nucleus and entered the cytoplasm of the cell. After associating with CHMP3 RNA in the cytoplasm, the transposable elements brought the code for CHMP3 back into the nucleus and reintegrated it into the genome. When the extra versions of CHMP3 were copied into the genome, they were not copied perfectly by the cellular machinery, and thus changes were introduced into the sequences. Upon a first look at the data, these imperfections seemed to render them nonfunctional ‘pseudogenes’. But as Elde’s team delved into the mystery of why squirrel monkeys had so many copies of CHMP3, an intriguing story emerged.

The discovery of pseudogenes is not wholly uncommon. There are more than 500,000 LINE-1 retrotransposons in the human genome11, and these elements have scavenged and reinserted the codes for other proteins inside the cell as well. Unlike with the endogenous retroviral elements in the genome, which can be clearly traced back to ancient viruses, the origin of LINE-1 retrotransposons is murky. However, both types of transposable elements contain the code for an enzyme called reverse transcriptase, which theoretically enables them to reinsert genetic code into the genome in the cell nucleus. This enzyme is precisely what allowed LINE-1 activity to copy CHMP3 back into the genome of the squirrel-monkey ancestor.

Elde couldn’t stop thinking about the mystery of why squirrel monkeys had multiple variants of CHMP3. He knew that in humans, the functional variant of the CHMP3 gene makes a protein that HIV uses to bud off of the cell membrane and travel to and infect other cells of the body. A decade ago, a team of scientists used an engineered vector to prompt human cells in a dish to produce a truncated, inoperative version of the CHMP3 protein and showed that the truncated protein prevented HIV from budding off the cells12. There was hope that this insight would yield a new way of treating HIV infection and so prevent AIDS. Unfortunately, the protein also has a role in allowing other important molecular signals to facilitate the formation of packages that bud off of the cell membrane. As such, the broken CHMP3 protein that the scientists had coaxed the cells to produce soon caused the cells to die.

Given that viruses such as HIV use a budding pathway that relies on normal CHMP3 protein, Elde wondered whether the extra, altered CHMP3 copies that squirrel monkeys carry confers some protection against viruses at the cellular level. He coordinated with researchers around the globe, who sent squirrel-monkey blood from primate centers as far-reaching as Bastrop, Texas, to French Guiana. When Elde’s team analyzed the blood, they found that the squirrel monkeys actually produced one of the altered versions of CHMP3 they carry. This finding indicated that in this species, one of the CHMP3 copies was a functional pseudogene, making it more appropriately known as a ‘retrogene’. In a further experiment, Elde’s group used a genetic tool to coax human kidney cells in a dish to produce this retrogene version of CHMP3. They then allowed HIV to enter the cells, and found that the virus was dramatically less able to exit the cells, thereby stopping it in its tracks. By contrast, in cells that were not engineered to produce the retrogene, HIV was able to leave the cells, which means it could theoretically infect many more.

In a separate portion of the experiment Elde’s group demonstrated that whereas human cells tweaked to make the toxic, truncated version of CHMP3 (the kind originally engineered a decade ago) die, cells coaxed to make the squirrel-monkey retrogene version of CHMP3 can survive. And by conducting a further comparison with the truncated version, Elde found that the retrogenewhat he calls retroCHMP3in these small primates had somehow acquired mutations that resulted in a CHMP3 protein containing twenty amino acid changes. It’s some combination of these twenty points of difference in the protein made by the retrogene that he thinks makes it nontoxic to the cell itself but still able to sabotage HIV’s efforts to bud off of cells. Elde presented the findings, which he plans to publish, in February at the Keystone Symposia on Viral Immunity in New Mexico.

The idea that retroCHMP3 from squirrel monkeys can perhaps inhibit viruses such as HIV from spreading is interesting, says Michael Emerman, a virologist at the Fred Hutchinson Cancer Research Center. Having an inhibitor of a process always helps you understand what’s important for it, Emerman explains. He adds that it’s also noteworthy that retroCHMP3 wasn’t toxic to the cells, because this finding could inspire a new antiviral medicine: It could help you to design small molecules or drugs that could specifically inhibit that part of the pathway that’s used by viruses rather than the part of the pathway used by host cells.

Akiko Iwasaki, an immunologist at the Yale School of Medicine in New Haven, Connecticut, is also optimistic that the finding will yield progress. What is so cool about this mechanism of HIV restriction is that HIV does not bind directly to retroCHMP3, making it more difficult for the virus to overcome the block imposed by retroCHMP3, Iwasaki says. Even though humans do not have a retroCHMP3 gene, by understanding how retroCHMP3 works in other primates, one can design strategies to mimic the activity of retroCHMP3 in human cells to block HIV replication.

Elde hopes that, if the findings hold, cells from patients with HIV infection might one day be extracted and edited to contain copies of retroCHMP3, and then reintroduced into these patients. Scientists have already used a similar cell-editing approach in clinical trials to equip cells with a variant of another gene, called CCR5, that prevents HIV from entering cells. In these experiments, patients have received infusions of their own cellsmodified to carry the rare CCR5 variant. But although preliminary results indicate that the approach is safe, there is not enough evidence yet about its efficacy. (Another point of concern is that people with the rare, modified version of the CCR5 gene might be as much as 13 times more susceptible to getting sick from West Nile virus than those with the normal version of this gene13.) By editing both retroCHMP3 and the version of CCR5 that prevents HIV entry into cells, Elde suggests, this combination of gene edits could provide a more powerful way of modifying patient cells to treat HIV infection.

You could imagine doing a sort of cocktail genetic therapy in order to block HIV in a way that the virus can’t adapt around it, Elde says. His team also plans to test whether retroCHMP3 has antiviral activity against other viruses, including Ebola.

The investigations into how pseudogenes and retrogenes might influence health are ongoing. And there is mounting evidence that the LINE-1 elements that create them are more active than previously thought. In 2015, for example, scientists at the Salk Institute in California reported a previously unidentified region of LINE-1 retrotransposons that are, in a way, supercharged. The region that the researchers identified encodes a protein that ultimately helps the retrotransposons to pick up bits of DNA in the cell cytoplasm to reinsert them into the genome14. The same region also enhances the ability of LINE-1 elements to jump around the genome and thus create variation, adding weight to the idea that these elements might have an underappreciated role in human evolution and in creating diversity among different populations of people.

The active function of transposable elements is more important than many people realize, according to John Coffin, a retrovirus researcher who divides his time between his work at the US National Cancer Institute in Frederick, Maryland, and Tufts University in Boston. They canand havecontributed in important ways to our biology, he says. I think their role in shaping our evolutionary history is underappreciated by many evolutionary biologists.

Squirrel monkeys are not the only animals that might reap protection against viral invaders thanks in part to changes in the genome caused by transposable elements. In 2014, Japanese scientists reported on a chunk of Borna virus embedded in the genome of ground squirrels (Ictidomys tridecemlineatus). The team’s results from cellular experiments suggest that this transposed chunk encodes a protein that might interfere with the pathogenicity of external Borna viruses that try to invade these animals15. Humans also have embedded chunks of Borna virus in their genomes. But we don’t have the same antiviral version that the ground squirrels haveand we might therefore be less protected against invading Borna viruses.

Other studies of endogenous viruses might have clearer implications for human health, and so scientists are looking at the activity of these transposable elements in a wide range of other animals, including the house cat. This past October, another group of Japanese researchers found that viruses embedded in the genomes of domesticated cats have some capacity to replicate. This replication was dependent on how well the feline cells were able to squelch the endogenous viruses in the genome through a silencing process called methylation16. But perhaps the most striking example of a replicating endogenous retrovirus is in koalas. In the 1990s, veterinarians at Dreamworld, a theme park in Queensland, Australia, noticed that the koalas were getting lymphoma and other cancers at an alarming rate. The culprit turned out to be a retrovirus that was jumping around in the animals’ genomes and wreaking havoc. Notably, koalas in the south of the country showed no signs of the retrovirus, which suggests that the virus had only recently begun to integrate into these animals’ DNA17.

The risks of transposable elements to human health are a concern when it comes to the tissue transplants we receive from other species, such as from pigs, which have porcine endogenous retroviruses. These embedded viruseswhich have the unfortunate abbreviation PERVscan replicate and infect human cells.

Transplants from pigs, for example, commonly include tissues such as tendons, which are used in ACL-injury repair. But these tissues are stripped of the pig cellsand thus of PERVsso that just the tissue scaffold remains. However, academic institutions and companies are actively designing new ways to use pig tissues in humans. Earlier this year, Smithfield Foods, a maker of bacon, hotdogs and sausages, announced it had launched a new bioscience unit to help supply pig parts to medical companies in the future. Meanwhile, George Church, a Harvard Medical School geneticist and entrepreneur, has formed a company called eGenesis Bio to develop humanized pigs for tissue transplantation. In March, the company announced that it had raised $38 million in venture funding. Church published a paper two years ago showing that his team had edited out key bits of 62 PERVs from pig embryos, disrupting the PERVs’ replication process and reducing their ability to infect human cells by 1,000-fold18.

Whereas Church and other scientists have tried disrupting endogenous retroviruses in animal genomes, researchers have also experimented with resurrecting them: a decade ago, a group of geneticists in France stirred up some controversy when the researchers recreated a human endogenous retrovirus by correcting the mutations that had rendered it silent in the genome for millennia. The scientists called it the ‘Phoenix’ virus, but it showed only a weak ability to infect human cells in the lab19. There was, perhaps unsurprisingly, pushback against the idea of resurrecting viruses embedded in our genomeno matter how wimpy the resulting viral creation.

But emerging data suggest that the retroviruses buried in the human genome might not be quite as dormant as we thought. The ability for these endogenous retroviruses to awaken from the genome is more widespread than has been previously appreciated, says virologist Rene Douville at the University of Winnipeg in Canada. She views this phenomenon as being the rule, rather than the exception within the cell: These retroelements are produced from the genome as part of the cell’s normal function to varying degrees.

Interestingly, the cellular machinery involved in keeping cancer at bay might also have a connection to transposable elements. One in three binding sites in the human genome for the important tumor-suppressor protein p53 are found within endogenous retroviruses in our DNA20. And last year, a team led by John Abrams at University of Texas Southwestern Medical Center in Dallas offered preliminary evidence that p53 might do its work by perhaps keeping embedded retroelements in check21.

When I first started openly publicly talking about this story, some of my colleagues here who are in the cancer community said, ‘Hey, that’s cute, but it can’t be true. And the reason it can’t be true is that we would know this already,’ Abrams recalls. The reason it wasn’t seen before, he explains, is that many genetic analyses throw out repeated sequenceswhich often consist of retroelements. So his team had to go dumpster diving in the genetic databases for these sequences of interest to demonstrate the link to p53. Abrams suspects that when p53 fails to keep retrotransposons at bay, tumors might somehow arise: The next question becomes, ‘How do you get to cancer?’ Abrams says that this is an example of what he calls transposopathies.

Not all scientists are convinced of a causal link between p53 and retroelements in cancer. My question is, if p53 is so vital in suppressing retrotransposon activity in cancer, why do we not find evidence of dysregulated retrotransposons inserting copies of themselves into the tumor genome more often? asks David Haussler, a genomics expert at the University of California, Santa Cruz. Most tumors have p53 mutations, yet only a very small percentage of tumors show evidence of significantly dysregulated rates of new retrotransposon copy insertion.

Still, there are others interested in exploring whether ancient viruses might reawaken in cancer or have some other role in this disease. Five years ago, scientists at the University of Texas MD Anderson Cancer Center reported that a type of viral protein produced by the human endogenous retrovirus type K (HERV-K) is often found on the surface of breast cancer cells. In a mouse experiment, they showed that cancers treated with antibodies against this protein grew to only one-third of the size of tumors that did not receive this therapy22.

But some cancer scientists are thinking about co-opting endogenous retroviruses to use against cancer. Paul Bieniasz of the Rockefeller University in New York City gained insight into this approach by studying human endogenous retrovirus type T (HERV-T)an ancient virus that spread for 25 million years among our primate ancestors until its extinction roughly 11 million years ago and at some point became fossilized in our DNA lineage. In April, his group found that a particular HERV-T encodes a protein that blocks a protein called monocarboxylate transporter 1, which is abundant on the surface of certain types of cancer cells23. It’s thought that monocarboxylate transporter 1 has a role in enabling tumors to grow. Blocking it could help to stymie the expansion of malignancies, Bieniasz speculates. He and his colleagues are now trying to build an ‘oncolytic virus’ that uses elements of HERV-T to treat cancer.

The idea that new viruses might still be trying to creep into our genomes is a scary one, even if they don’t appear very effective at achieving this. One of the most recent to integrate into our genome in a way that it is passed down from generation to generation is human endogenous retrovirus type K113 (HERV-K133), which sits on chromosome 19. It’s found in only about one-third of people worldwide, most of whom are of African, Asian or Polynesian background. And researchers say that it could have integrated into the genome as recently as 200,000 years ago6.

Although experts remain skeptical that a virus will integrate into the human genome again anytime soon, other transposable elements, such as LINE-1s, continue to move around in our DNA. Meanwhile, the field that Barbara McClintock seeded more than half a century ago is growing quickly. John Abrams, who is studying retroelements, says that we’re only just beginning to understand how dynamic the genome is. He notes that only recently have people begun to appreciate how the ‘microbiome’ of bacteria living in our guts can influence our health. We’re really an ecosystem, Abrams says of the gut, and the genome is the same way. There is the host DNAbelonging to usand the retro-elements it contains, he explains, and there’s this sort of productive tension that exists between the two.

This article is reproduced with permission and wasfirst publishedon July 11, 2017.

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Medicine’s Movable Feast: What Jumping Genes Can Teach Us about Treating Disease – Scientific American

Genetic test that predicts prognosis could benefit early-stage colon cancer patients – News-Medical.net

July 26, 2017

Early-stage colon cancer patients could benefit in the future from specific genetic tests that forecast their prognosis and help them make the right decision regarding chemotherapy. Two of the biomarkers involved are the MACC1 gene, high levels of which promote aggressive tumor growth and the development of metastasis, and a defective DNA mismatch repair (dMMR) system, which plays a role in tumor formation. Life expectancy is longer for patients with dMMR tumors and with low MACC1 gene activity.

In a study of around 600 stage II colon cancer patients (locally aggressive tumors without metastases), scientists at the Max Delbrck Center for Molecular Medicine (MDC) and the Charit – Universittsmedizin Berlin have shown for the first time that the MACC1 genetic test can help further differentiate between patients with defective repair mechanisms. The prognosis is as positive for those with low MACC1 gene expression as it is for patients with defective repair mechanisms: a 100 percent five-year survival rate. The genetic test may also have implications for the recommended course of treatment, as these patients would not benefit from chemotherapy.

The results of the Berlin study led by Prof. Ulrike Stein of MDC/Charit – Universittsmedizin Berlin were published in the journal Annals of Oncology. The study was done in cooperation with Hoffmann La-Roche (Switzerland and Germany) and Ventana Medical Systems (Tucson, United States), as well as the Walter and Eliza Hall Institute (Melbourne, Australia) and the University of Freiburg (Germany).

Blood tests can help predict chemotherapy success

Colon cancer is the second most common type of cancer in Germany, affecting around 60,000 male and female patients every year. The five-year survival rate averages 70 percent. Treatment success is largely dependent on whether the tumor is detected early on, whether it can be completely surgically removed, and whether it responds to chemotherapy.

In recent years, scientists have successfully identified genetic subtypes of malignant colon tumors, all of which carry a different prognosis for how the disease will develop. Up to 15 percent of these malignant tumors, for example, exhibit defective DNA repair mechanisms – known as DNA mismatch repair deficiency or dMMR. Another important biomarker is the gene MACC1 (metastasis-associated in colon cancer 1), which was identified by Ulrike Stein and her colleagues at MDC in 2009. There is now a patented blood test for MACC1 detection.

The five-year survival rate for patients with stage I-III colon cancer who exhibit low levels of MACC1 lies at 80 percent – in comparison to just 15 percent for patients with high MACC1 levels. “The blood test can indicate whether there is a higher risk of the tumor returning or metastasizing,” says Stein. “It helps with the difficult decision of whether early-stage patients should receive chemotherapy.” This now also includes patients in stage II of the disease with impaired DNA repair mechanisms.

In an editorial, also published in Annals of Oncology, scientists at Houston’s MD Anderson Cancer Center quote this study as further proof of how important it is to identify genetic subtypes and subtype combinations even in the early stages of the cancer, not least to help with prognosis and decisions regarding chemotherapy. They recommend that, in the future, genetic test results should be combined with further genetic and epigenetic data from patients, “in order to understand the prognostic value of the complex molecular scenarios of early-stage colon cancer.”

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Genetic test that predicts prognosis could benefit early-stage colon cancer patients – News-Medical.net

3 Genetics Tests To Improve Prenatal Screening – HuffPost

This article is authored by the Mayo Clinic Center for Individualized Medicine. The mission of the Center is to discover and integrate the latest in genomic, molecular and clinical sciences into personalized care for patients.

New technology is reshaping prenatal screening to assess the health of a developing baby. Now pregnant women can have their baby initially screened for genetic disorders, such as Down syndrome, through the use of a newer blood test that evaluates DNA present in the mothers blood stream. Another test for couples planning a family uses a single blood sample to assess whether future children might be at risk for developing a genetic disease.

Its an exciting time in perinatal testing, explains Myra Wick, M.D., Ph.D. DNA sequencing and molecular technology have improved and become more cost effective. These tests are important for family planning before pregnancy as well as planning for the care of a baby who is found to have a genetic disorder during pregnancy.

Researchers from Mayo Clinic and the Center for Individualized Medicine have helped implement several of these tests, which use a personalized medicine approach to perinatal screening. Three state-of-the-art perinatal genetic tests are becoming more widely available to expectant parents.

Mayo Medical Laboratories recently launched a blood test to screen for the most common chromosome disorders diagnosed in pregnancy, such as Down syndrome. Its known as a cell-free DNA test. It screens the mothers blood that contains DNA from the baby, looking for genetic disorders in the fetus. The new test generally has a higher detection rate and fewer false positives than traditional screening tests.

Prior to this new test, mothers had the option of traditional first trimester screening, which is a blood test and ultrasound, or second trimester screening, which is a blood test. In general, the cell free DNA blood test can be used in place of the traditional first and second trimester screening, explains Dr. Wick. It is important to remember that the cell free DNA testing is a screening test, and abnormal results should be followed up with additional testing.

The out-of-pocket cost for the new blood test varies depending on insurance coverage, and the specific laboratory performing the testing; a general estimate is approximately $350. Results are usually ready within one week.

2. Expanded carrier screening

In the past, couples had genetic screening based on family history of a genetic disorder, or if they were part of an ethnic group at risk for certain inherited diseases. Previous tests only screened for a small defined group of genetic disorders. Those tests didnt help couples who were uncertain of their ethnic heritage, plus the tests were very limited in scope.

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Its an exciting time in perinatal testing. DNA sequencing and molecular technology has improved and become more cost effective. These tests are important for family planning prior to pregnancy as well as planning for the care of a child who is found to have a genetic disorder during pregnancy. – Dr. Myra Wick

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Now couples may choose a more comprehensive test that looks for 100 or more genetic disorders. Its called expanded carrier screening. This test is done with a blood sample from each prospective parent.

Expanded carrier screening looks at multiple genes associated with genetic diseases. Most of the disorders included on an expanded carrier screen are inherited in an autosomal recessive manner. This means that the parents are carriers of the disorder, with one normal copy of the gene and one abnormal copy of the gene. Carriers of an autosomal recessive disorder do not typically have signs or symptoms of the disease. A child is affected with an autosomal recessive disorder when he or she inherits one abnormal copy of the gene from mom, and one abnormal copy of the gene from dad. Approximately 5% of couples who undergo expanded carrier screening are found to be carriers for the same disorder, and at risk for having an affected says Dr. Wick.

Depending upon insurance coverage, the test costs approximately $350. Test results are returned within one to two weeks.

3. Whole exome sequencing (WES)

In rare cases, an ultrasound during pregnancy reveals that the baby has several medical problems. Traditional genetic testing may not identify a diagnosis. Now whole exome sequencing (WES), which looks at most of the genes linked to growth and health, can be used to evaluate the fetuss condition. It can provide a diagnosis in 30 percent of cases.

For this testing, an amniocentesis is performed first to obtain DNA for genetic analysis.

We are beginning to use WES even before the baby is born. Results can be used to plan for care of an infant who may be born with several complex medical concerns. In addition, parents can use this information for future family planning, says Dr. Wick.

Whole exome sequencing is expensive, with typical costs of approximately $8,000, depending upon the specific test and insurance coverage. Results from this more complex screening usually take several weeks, depending upon the specific test being used.

Dr. Wicks suggests that you ask your health care provider about genetic testing and recommends that all prospective and expectant parents consult with a medical geneticist or genetic counselor before genetic screening.

If your provider is at a large medical center, genetic counseling should be available. At smaller facilities, your primary provider may order initial blood tests, but you may be referred to a larger facility if test results indicate you need genetic counseling.

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3 Genetics Tests To Improve Prenatal Screening – HuffPost

Phase 2/3 Trial of Elamipretide to Treat Barth Syndrome Now Enrolling Patients – Mitochondrial Disease News

A Phase 2/3 clinical trial of elamipretide,a potential treatment for a rare mitochondrial disease known asBarth syndrome, is now enrolling patients, the therapys developer,Stealth BioTherapeutics, announced.

The TAZPOWER study (NCT03098797) will be conducted in McKusick-Nathans Institute of Genetic Medicine, at the Johns Hopkins University School of Medicine, and is expected to include 12 patients, ages 12 or older, with genetically confirmed Barth syndrome and stable symptoms, butimpaired walking ability.

Our understanding of Barth syndrome and how it manifests has evolved significantly, but current treatment efforts are still limited to the management of symptoms, Hilary Vernon, anassistant professor of pediatrics at the McKusick-Nathans Institute and the studys primary investigator, said in a press release. The initiation of TAZPOWER represents an important milestone in the potential development of a disease-specific treatment option.

Barth syndrome is a rare inherited mitochondrial disease that is almost exclusive to males. This disease is characterized by cardiac abnormalities, skeletal muscle weakness, recurrent infections due to low white blood cell (immune cell) counts, and delayed growth. It is caused by caused by genetic mutations in the TAZ gene, which encodes the protein tafazzin that is essential for the normal functioning of mitochondria.

The severe problems experienced by patients with Barth syndrome are caused by misshapen and dysfunctional mitochondria, which reduce the energy production in the affected tissues. The resulting muscle weakness can lead to severe fatigue, heart failure and death, said Doug Weaver, chief medical officer at Stealth. In this study, we hope to show that elamipretide may have clinical benefit by improving function in these affected mitochondria.

Elamipretidewas designed to restore mitochondrias ability to work as the cells power source. Due to its capacity to penetrate the inner membrane of mitochondria, the therapy as the potential to reduce the levels of damaging oxidative stress produced by mitochondrias dysfunctional activity.

TAZPOWER trial is a placebo-controlled crossover study, designed to evaluate the effects of daily administration of elamipretide in patients with Barth syndrome. All participants will receive single daily subcutaneous injections of elamipretide or placebo for 12 weeks, followed by a four-week wash-out period. This will then be followed by additional 12 weeks of therapy, but this time the patients will switch the treatment received, with those previously givenelamipretide now receivinga placebo and vice-versa.

The drugs efficacy will be measured by changes in the distance that patients are able to walk during the 6-minute walk test (6MWT). Secondary endpoints will include other functional assessments (of muscle strength, balance, etc.), patient-reported outcomes, and overall treatment safety.

This study underscores our commitment to develop elamipretide for the treatment of rare genetic mitochondrial diseases, said Reenie McCarthy, Stealths chief executive officer.

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Phase 2/3 Trial of Elamipretide to Treat Barth Syndrome Now Enrolling Patients – Mitochondrial Disease News


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