StemCell Therapy

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

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

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 symposiumPhoto 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)

Xconomy Boston

One day after the release of a Nature Medicine paper warning of the potential hazards of testing CRISPR-Cas9 gene editing in humans, Homology Medicines, a startup advancing a different genetic surgery technique, has just grabbed a big round of funding to make its own clinical push.

Homology, of Bedford, MA, wrapped up an $83.5 million Series B round this morning. A wide group of investors led by Deerfield Management provided the funding, bringing the companys total amount raised to a whopping $127 million since it was formed last year.

Homology is making the bold claim that its underlying science, technology it calls AMEnDR, is a better version of existing gene editing methods, among them the CRISPR-Cas9 technology that has taken the scientific research world by storm and has led to the formation of three now publicly traded companies, Editas Medicine (NASDAQ: EDIT), Intellia Therapeutics (NASDAQ: NTLA), and CRISPR Therapeutics (NASDAQ: CRSP).

CRISPR gene editing is a two-part biological system that researchers can use to help irreversibly alter DNA. The three companies are involved in a high-stakes race to use the technology to develop human therapeutics, with the first clinical trials expected to begin next year. Yet one of the fears involved in bringing the technology to human trials is the possibility of off-target effectsa genetic surgery error that causes irreparable damage, like cancer. One of the fields pioneers, Feng Zhang of the Broad Institute of MIT and Harvard, just co-authored a paper in Nature Medicine urging caution about the rush to move forward. Zhang and colleague David Scott argued that researchers should analyze patients DNA before giving them CRISPR-based drugs, citing the myriad differences between each persons genetic makeup.

Homology isnt using CRISPR, like its publicly traded rivals. Instead, its recreating a natural biological process known as homologous recombination, which cells in humans and other species do to repair DNA damage or, in the case of bacteria, to improve their genetic diversity. In homologous recombination, one chromosome essentially swaps one short DNA sequence for another similar one. Homology aims to engineer a piece of healthy DNA, pack it into a type of adeno-associated virus, or AAVa delivery tool commonly used in gene therapy and gene editing technologiesand infuse it into the body. The virus carrying the DNA locks on to the cell that needs a genetic fix, enters it, and releases its DNA payload. The healthy DNA then swaps places with the faulty gene inside the patients cells. If and when the cells divide, the new cells would carry the fixed gene, not the faulty one. One potential benefit of this approach is there may be less likelihood of an off-target error, like mutations in the target DNA that cause cancer, than with CRISPR.

Thats the hope, but the technology hasnt been tested in humans as of yet. With the new cash, however, Homology is getting a shot to try. In a statement, Homology CEO Arthur Tzianabos said the funding will help Homology bring its first drug candidate toward the clinic, though he didnt specify how long that might take. The company is focusing on rare diseasesno surprise given Tzianabos, chief operating officer Sam Rasty, and chief scientific officer Albert Seymour all worked with one another at rare disease giant Shire (NASDAQ: SHPG). According to its website, the company will develop therapies for inborn errors of metabolism, and Duchenne muscular dystrophy and cystic fibrosis are among its potential targets as well. (Duchenne and cystic fibrosis are early targets of CRISPR-based medicines as well.)

Fidelity Management and Research, Novartis, Rock Springs Capital, HBM Healthcare Investments, Arch Venture Partners, Temasek, 5AM Ventures, Maverick Ventures, Vida Ventures, Vivo Capital, and Alexandria Venture Investments also took part in the funding. Heres more on Homology, and gene editing with CRISPR-Cas9.

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com

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Homology Med Bags $83.5M More, Fueling Push For Gene Editing Twist - Xconomy

At the meeting, the panel of experts did not question the lifesaving potential of the treatment in hopeless cases. But they raised concerns about potentially life-threatening side-effects short term worries about acute reactions like those Emily experienced, and longer-term worries about whether the infused cells could, years later, cause secondary cancers or other problems. So far, no such long-term problems have been detected, but not enough time has passed to rule them out.

Another parent at the meeting, Don McMahon, described his son Connors grueling 12 years with severe and relapsing leukemia, which started when he was 3. Mr. McMahon displayed painful photographs of Connor, bald and intubated during treatment. And he added that chemotherapy had left his son infertile. A year ago, the family was preparing for a bone-marrow transplant when they learned about T-cell treatment. Connor underwent the cell treatment at Duke University, and he has since returned to playing hockey. Compared with standard treatment, which required dozens of spinal taps and painful bone-marrow tests, the T-cell treatment was far easier to tolerate, Mr. McMahon said, and he urged the panel to vote for approval.

The treatment was developed by researchers at the University of Pennsylvania and licensed to Novartis.

Use will not be widespread at first, because the disease is not common. It affects only 5,000 people a year, about 60 percent of them children and young adults. Most children are cured with standard treatments, but in 15 percent of the cases like Emilys and Connors the disease does not respond, or it relapses.

Analysts predict that these individualized treatments could cost more than $300,000, but a spokesman for Novartis declined to specify a price.

Because the treatment is complex and patients need expert care to manage the side effects, Novartis will initially limit its use to 30 or 35 medical centers where staff will be trained and approved to administer it, the company said.

As to whether the treatment, known as CTL019, will be available in other countries, a Novartis spokeswoman said by email: Should CTL019 receive approval in the U.S., it will be the decision of the centers whether to receive international patients. We are working on bringing CTL019 to other countries around the world. She added that the company would file for approvals in the European Union later this year.

The treatment requires removing millions of a patients T-cells a type of white blood cell and genetically engineering them to kill cancer cells. The technique employs a disabled form of H.I.V., the virus that causes AIDS, to carry new genetic material into the T-cells to reprogram them. The process turbocharges the T-cells to attack B-cells, a normal part of the immune system that turn malignant in leukemia. The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells.

The altered T-cells called chimeric antigen receptor cells are then dripped back into the patients veins, where they multiply and start fighting the cancer.

Dr. Carl H. June, a leader of the University of Pennsylvania team that developed the treatment, calls the turbocharged cells serial killers. A single one can destroy up to 100,000 cancer cells.

In studies, re-engineering cells for treatment sometimes took four months, and some patients were so sick that they died before their cells came back. At the meeting, Novartis said the turnaround time was now down to 22 days. The company also described bar-coding and other procedures used to keep from mixing up samples once the treatment is conducted on a bigger scale.

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FDA Panel Recommends Approval for Gene-Altering Leukemia Treatment - New York Times

Killer T cells surround a cancer cell. Credit: NIH

Early phase Northwestern Medicine research has demonstrated a potential new therapeutic strategy for treating deadly glioblastoma brain tumors.

The strategy involves using lipid polymer based nanoparticles to deliver molecules to the tumors, where the molecules shut down key cancer drivers called brain tumor initiating cells (BTICs).

"BTICs are malignant brain tumor populations that underlie the therapy resistance, recurrence and unstoppable invasion commonly encountered by glioblastoma patients after the standard treatment regimen of surgical resection, radiation and chemotherapy," explained the study's first author, Dr. Dou Yu, research assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine.

The findings were published in the journal Proceedings of the National Academy of Sciences.

Using mouse models of brain tumors implanted with BTICs derived from human patients, the scientists injected nanoparticles containing small interfering RNA (siRNA)short sequences of RNA molecules that reduce the expression of specific cancer promoting proteinsdirectly into the tumor. In the new study, the strategy stopped tumor growth and extended survival when the therapy was administered continuously through an implanted drug infusion pump.

"This major progress, although still at a conceptual stage, underscores a new direction in the pursuit of a cure for one of the most devastating medical conditions known to mankind," said Yu, who collaborated on the research with principal investigator Dr. Maciej Lesniak, Michael J. Marchese Professor of Neurosurgery and chair of neurological surgery.

Glioblastoma is particularly difficult to treat because its genetic makeup varies from patient to patient. This new therapeutic approach would make it possible to deliver siRNAs to target multiple cancer-causing gene products simultaneously in a particular patient's tumor.

In this study, the scientists tested siRNAs that target four transcription factors highly expressed in many glioblastoma tissuesbut not all. The therapy worked against classes of glioblastoma BTICs with high levels of those transcription factors, while other classes of the cancer did not respond.

"This paints a picture for personalized glioblastoma therapy regimens based on tumor profiling," Yu said. "Customized nanomedicine could target the unique genetic signatures in any specific patient and potentially lead to greater therapeutic benefits."

The strategy could also apply to other medical conditions related to the central nervous systemnot just brain tumors.

"Degenerative neurological diseases or even psychiatric conditions could potentially be the therapeutic candidates for this multiplexed delivery platform," Yu said.

Before scientists can translate this proof-of-concept research to humans, they will need to continue refining the nanomedicine platform and evaluating its long-term safety. Still, the findings from this new research provide insight for further investigation.

"Nanomedicine provides a unique opportunity to advance a therapeutic strategy for a disease without a cure. By effectively targeting brain tumor initiating stem cells responsible for cancer recurrence, this approach opens up novel translational approaches to malignant brain cancer," Lesniak summed up.

Explore further: Cold virus, stem cells tested to destroy deadly brain cancer

More information: Dou Yu et al, Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1701911114

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Nanomedicine opens door to precision medicine for brain tumors - Phys.Org

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Twin study reveals strong genetic influences on how infants visually explore social world

Using eye-tracking technology, researchers at Washington University School of Medicine in St. Louis and Emory University School of Medicine in Atlanta have found compelling evidence that genetics plays a major role in how children look at the world and whether they have a preference for gazing at peoples eyes and faces or at objects. The discovery adds new detail to understanding the causes of autism spectrum disorder. Studying twins, the researchers found that where babies focus their eyes is under stringent genetic control.

New research has uncovered compelling evidence that genetics plays a major role in how children look at the world and whether they have a preference for gazing at peoples eyes and faces or at objects.

The discovery by researchers at Washington University School of Medicine in St. Louis and Emory University School of Medicine in Atlanta adds new detail to understanding the causes of autism spectrum disorder. The results show that the moment-to-moment movements of childrens eyes as they seek visual information about their environment are abnormal in autism and under stringent genetic control in all children.

The study is published online July 12 in the journal Nature.

Now that we know that social visual orientation is heavily influenced by genetic factors, we have a new way to trace the direct effects of genetic factors on early social development, and to design interventions to ensure that children at risk for autism acquire the social environmental inputs they need to grow and develop normally, said lead author John N. Constantino, MD, the Blanche F. Ittleson Professor of Psychiatry and Pediatrics at Washington University. These new findings demonstrate a specific mechanism by which genes can modify a childs life experience. Two children in the same room, for example, can have completely different social experiences if one carries an inherited tendency to focus on objects while the other looks at faces, and these differences can play out repeatedly as the brain develops early in childhood.

The researchers studied 338 toddlers ages 18 to 24 months using eye-tracking technology, developed at Emory, allowing them to trace young childrens visual orientation to faces, eyes or objects as the children watched videos featuring people talking and interacting.

The children, who were part of the Missouri Family Registry, a database of twins that is maintained at Washington University School of Medicine, included 41 pairs of identical twins such twins share 100 percent of their DNA and 42 sets of fraternal twins who share only about 50 percent of their DNA. In addition, the researchers studied 84 unrelated children and 88 children diagnosed with autism spectrum disorder.

Constantino, with fellow investigators Warren R. Jones, PhD, and Ami Klin, PhD, of Emory University School of Medicine, evaluated the eye-tracking data. Each twin was tested independently, at different times, without the other twin present.

How much one identical twin looked at another persons eyes or face was almost perfectly matched by his or her co-twin. But in fraternal twins, eye movements in one twin accounted for less than 10 percent of the variation in the eye movements of his or her co-twin. Identical twins also were more likely to move their eyes at the same moments in time, in the same directions, toward the same locations and the same content, mirroring one anothers behavior to within as little as 17 milliseconds. Taken together, the data indicate a strong influence of genetics on visual behavior.

The moment-to-moment match in the timing and direction of gaze shifts for identical twins was stunning and inferred a very precise level of genetic control, said Constantino, who directs the William Greenleaf Eliot Division of Child and Adolescent Psychiatry at Washington University. We have spent years studying the transmission of inherited susceptibility to autism in families, and it now appears that by tracking eye movements in infancy, we can identify a key factor linked to genetic risk for the disorder that is present long before we can make a clinical diagnosis of autism.

The effects persisted as the children grew. When the twins were tested again about a year later, the same effects were found: Identical twins remained almost perfectly matched in where they looked, but fraternal twins became even more different than they were when initially evaluated.

Autism spectrum disorder is a lifelong condition that affects about 1 in 68 children in the United States. It is known to be caused by genetic factors, and earlier work by the Emory University team had shown that babies who look progressively less at peoples eyes, beginning as early as 2-6 months of age, have an elevated risk for autism. Meanwhile, Constantino and others in the group have studied how subtle behaviors and symptoms that characterize autism aggregate in the close relatives of individuals with autism, as a way to identity inherited susceptibilities that run in families and contribute to autism risk.

Studies like this one break new ground in our understanding of autism spectrum disorder: Establishing a direct connection between the behavioral symptoms of autism and underlying genetic factors is a critical step on the path to new treatments, said Lisa Gilotty, PhD, chief of the Research Program on Autism Spectrum Disorders at the National Institute of Mental Health, which provided support for the study in tandem with the Eunice Kennedy Shriver Institute of Child Health and Human Development.

Those new treatments could include interventions that motivate very young children to focus their gazes more on faces and less on objects.

Testing infants to see how they are allocating visual attention represents a new opportunity to evaluate the effects of early interventions to specifically target social disengagement, as a way to prevent the most challenging disabilities associated with autism, said senior author Warren R. Jones, PhD, director of autism research at the Marcus Autism Center at Emory. Such interventions might be appropriate for infants showing early signs of risk or those who have been born into families in which autism has affected close relatives. In addition, learning why some infants who tend to not look at eyes and faces develop without social disability is another priority.

The small percentage of healthy children who tended to avoid looking at eyes and faces may provide researchers with insight on how to successfully compensate for those tendencies and therefore inform the development of higher-impact interventions that will produce the best possible outcomes for infants with inherited susceptibility to autism.

In addition to Constantino, the research team at Washington Universityincluded Anne L. Glowinski, MD, a professor of child psychiatry and associate director of child and adolescent psychiatry;Natasha Marrus, MD, PhD, an assistant professor of child psychiatry; and Stefanie F. Kennon-McGill, PhD, a postdoctoral research associate in psychiatry.

As identical twins watched videos, they almost always looked for the same things at the same times and in the same places. Where gazes fell is marked by the plus signs. Fraternal twins didnt match as well as identical twins, indicating that genes control where children look.

Constantino JN, Kennon-McGill S, Weichselbaum C, Marrus N, Haider A, Glowinski AL, Gillespie S, Klaiman C, Klin A, Jones W. Infant viewing of social scenes is under genetic control and is atypical in autism. Nature. Published online July 12, 2017.

This work was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health of the National Institutes of Health (NIH), grant numbers HD068479 and U54 HD087011 (to Constantino and the Intellectual and Developmental Disabilities Research Center at Washington University) and MH100029 (to Jones and Klin at Emory). Other support was provided by the Missouri Family Register, a joint program of Washington University and the Missouri Department of Health and Senior Services.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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In autism, genes drive early eye gaze abnormalities - Washington University School of Medicine in St. Louis

Precision medicine is, ironically, an imprecise term.

As it is often used today, the phrase suggests that precision is novel to the practice of medicine, and to many, it means incorporating sophisticated genetic testing into its practice.

The term can even suggest that there are now possibilities of miracle cures that were never possible before.

Sometimes healthcare organizations encourage that attitude through their marketing and advertising, but to a degree, that kind of thinking more represents hype than substance.

And while genetic testing and the information it can provide can help better tailor treatment options for individual patients, especially in cancer care, experts say healthcare executives and clinicians must be careful not to encourage false hope among vulnerable patients and their families.

Yet in a time of rapid evolution of more precise and tailored treatment options, executives and clinicians are charged with divining the difficult calculus between the possible and the practical in their precision medicine organizational structure and service offerings.

In reality, precision has always been the goal of physicians as medicine has evolved over the past couple of hundred years, says Robert Mennel, MD, director of the Baylor Precision Medicine Institute in Dallas.

"In some areas we're there. We have well-accepted tests for certain diseases that, if you're not using them, I would consider to be malpractice in many situations," he says.

However, even top-level academic medicine is still quite far away from being able to look at an individual's whole genome and predict a therapy for every disease.

"But the promise of precision medicine is there, and medicine 10 years from now is going to be quite different than it is now," he says.

One area where genetic testing is ready for prime time is in noninvasive prenatal testing, says Scott A. Beck, administrator of the Center for Individualized Medicine at the Mayo Clinic in Rochester, Minn.

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Precision Medicine: Integration May Be Closer Than You Think - HealthLeaders Media

Mouse intestinal organoids that scientists genetically engineered to study colon cancer. Using gene editing technology, the investigators fused together the genes Ptprk and Rspo3 to determine their effect on cancer development. Credit: Cornell University

Genetic mutations caused by rearranged chromosomes drive the development and growth of certain colorectal cancers, according to new research conducted by Weill Cornell Medicine investigators.

Many of the genetic mutations present in colorectal cancer have been known for decades. But their exact role in cancer's development and progression has not been clear. "We knew that these mutations existed, but not whether they contribute to the disease," said Lukas Dow, an assistant professor of biochemistry in medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. "So we are interested in whether they are actually driving cancer and whether they can potentially be targets for drugs that treat it."

In a paper published July 11 in Nature Communications, Dow and his colleagues describe how large pieces of chromosomes are deleted or inverted, resulting in new, mutated so-called fusion genes created from parts of two other genes that are responsible for the formation of some colon cancers.

The researchers used the gene editing technology CRISPR, which allows scientists to easily alter any piece of DNA in an organism, to cut the DNA in normal human intestinal cells and create fusion genes. In this way, they engineered the genetic mutations in two genes Rspo2 and Rspo3 known to be associated with colorectal cancer. They then created mice containing these genes to study the genes' effect on colon cancer development.

Though CRISPR has received a lot of attention in the last several years, this is the first time the tool has been used this way. "We created the first CRISPR-based transgenic animal model for inducing large-scale chromosomal rearrangements," Dow said.

These chromosomal rearrangements in the Rspo genes did in fact initiate growth of colon cancer in the mice. The mice containing the engineered genes developed multiple precancerous tumors that are the precursors to colorectal cancer. "This is the first evidence that these specific fusions can drive tumor development," Dow said.

Dow's team went on to treat the mice that developed cancer with an experimental drug, LGK974, which blocks a protein necessary for Rspo fusion genes to cause disease. "The tumors shrank and the mice were fine as long as they continued to take LGK974," Dow said. In addition, the drug only suppressed growth of the cancer cells; it had no obvious negative effect on healthy cells in the mouse intestine.

The study's results hold particular promise for the treatment of colorectal cancer in humans, Dow said. This form of cancer has historically been a difficult disease to treat. Chemotherapy drugs have limited impact against colorectal cancer and developing targeted therapies drugs that target aspects of cancer cells that make them different from healthy cells has proven difficult. "Our results give us confidence that if we can deliver LGK974 effectively to patients with these fusion genes," Dow said, "then we should be able to see some tumor response with these targeted agents."

Explore further: Novel gene editing approach to cancer treatment shows promise in mice

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'Fusion genes' drive formation and growth of colorectal cancer - Medical Xpress

Whenever biopharmaceutical experts and policymakers discuss medical innovation, they seem to focus only on drug discovery and development and access. While these aspects of innovation are critical to ensuring patients have safe and effective treatments, they dont provide a complete picture of the biopharmaceutical innovation model and the total investment needed to get the right medicine to the right patient at the right time. Whats missing? An understanding of the role of biopharmaceutical manufacturing and the need for a supportive policy environment in order to ensure the United States maintains its place as the leader in discovering, developing and delivering innovative medicines.

In the past decade, manufacturing has become an even more complex element of the biopharmaceutical innovation ecosystem as there have been several paradigm shifts in clinical treatments and pharmacology that make drug manufacturing significantly more challenging. First, therapeutic innovations previously developed to treat millions of patients the so-called blockbuster medicines have been replaced by the precision medicine model. This model integrates genetic information to help researchers understand which particular subgroup of patients will most likely benefit from a specific treatment. This scientific progress is leading to the development of medicines targeted for much smaller patient populations. Thus, biopharmaceutical companies now need to manufacture smaller batches and incorporate shorter production lines into their manufacturing process, which means they need to be more nimble and think beyond just efficiency to ensure production levels match the new innovative landscape in their manufacturing practices.

Second, diseases today are more often managed with medicines administered through intricate delivery systems. Complex therapies deliver important drugs directly to the site of the disease by bypassing traditional modes of delivery through oral intake. So now manufacturers have to think about how to make both the delivery device as well as the medicine.

Third, certain diseases are managed or prevented through biologics or vaccines. Unlike synthesized medicines which are made by combining specific chemical ingredients in a laboratory environment, these therapies are derived from living cell lines which cannot be fully characterized by traditional methods in a lab. For biologics and vaccines, the final product is influenced by the manufacturing process as the product is the process. An example of a therapy that requires this type of manufacturing complexity is a breakthrough vaccine for pneumococcal diseases. You may wonder what does it take to manufacture a single dose of that vaccine? It takes no less than 2.5 years, the collaboration of 1,700 researchers, engineers and other manufacturing experts, more than 400 raw materials and 678 quality tests in 581 steps to produce a single dose. Any minute deficiency in this long and laborious manufacturing process and/or ingredient integrity could possibly lead to failure.

Beyond better health, the benefit of manufacturing excellence is also captured in the economic value it generates for local communities in states all across the country. In the United States alone, there are close to 300,000 biopharmaceutical manufacturing jobs, with an average salary of close to $100,000 annually. This average salary is in the top 2 percent of all manufacturing jobs in the U.S. Pfizer currently has 17 manufacturing sites in 11 states and Puerto Rico that employ more than 12,000 people, and has invested $2 billion in these sites over the past five years. Estimates put Pfizers contribution to both direct and indirect jobs in the U.S. at 51,000.

The Pfizer facilities are not only responsible for manufacturing safe and innovative medicines, but some of the sites also produce active product ingredients. The API is the actual substance or raw material used to produce the medicine that patients consume. In fact, the Pfizer facility in Kalamazoo, Mich., is so cost-efficient that it manufactures APIs for methylprednisolone that Pfizer then sells to manufacturers in China and India, something not commonly observed in other traditional manufacturing sectors.

To make biopharmaceutical manufacturing a centerpiece of U.S. economic growth, policymakers need to address a few policy hurdles. First, they need to reform the U.S. tax code to encourage companies to further invest in U.S. pharmaceutical manufacturing. Next, the Food and Drug Administration ought to forge a proactive partnership with industry to develop practical regulatory solutions to advance and encourage domestic biopharmaceutical manufacturing expertise while protecting world-class quality control and good manufacturing processes. Lastly, the federal government needs to ensure appropriate and timely implementation of Section 3016 of the 21st Century Cures Act, which allows the FDA to issue grants to further the study of continuous manufacturing of drugs and biologics.

In an effort to get important medicines to patients in need, biopharmaceutical companies discover, develop, manage access and manufacture medicines. The innovation cycle is not complete if a company is not able to appropriately navigate the complicated yet crucial manufacturing process. A pro-active, supportive policy environment is the linchpin to ensuring the United States remains at the forefront of biopharmaceutical innovation and manufacturing.

Robert Popovian is the vice president of Pfizer U.S. Government Relations. He has two decades of experience in the biopharmaceutical health care industry and has published and presented extensively on the impact of pharmaceuticals and health care policies on health care costs and clinical outcomes.

Morning Consult welcomes op-ed submissions on policy, politics and business strategy in our coverage areas. Updated submission guidelines can be foundhere.

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The Future of Manufacturing a Medicine in America - Morning Consult

Outside of evolutionary biology, the human body is often spoken of as a miracle of engineering. But those more familiar with its workings point out evolution is no perfectionist, often favoring clunky ad hoc solutions over thosemore elegant in design. In fact, the comparison of evolution to a gambler might be the most apt, and nowhere is this more evident than in reference to genetic diseases like hemophilia. Now a recent study published in the Annals of Internal Medicine suggests far more people than previously thought are carrying variants of rare genetic diseases and could force us to redefine what is considered a healthy genome.

Genetic disorders are those resulting from mutations in ones DNA, often with horrendous results. Previously, scientists believedgenetic disorders were present in only a small fraction of the human population, 5 percent or less. After all, a population riven with genetic mistakes would quickly die out, or so went the logic. However, the present study puts the fraction of people with mutations linked to genetic diseases at something closer to 20 percent.

But is nature really so clumsy as to allow a veritable swarm of deleterious mutations to slip through her quality control mechanisms? It turns out many genetic disorders hide secret advantages. Take a person with the mutation that causes sickle cell anemia. A single copy of the mutation for sickle cellanemiaactually protects against the disease malaria. Its only if someone receivestwo copies of the defective gene that the problematic form of sickle cellanemia results. With many genetic disorders, nature seems to be hedging her bets, allowing some defects to slip through if they can provide a survival advantage to the population at large.

Counterintuitively, an individual suffering from a rare genetic disease may represent a successful population-level response to a given environment. This dance between genes and environments is at the heart of what we think of as health. But for most of history, medicine has considered the well being of an individual in isolation from population-level genetics. A more nuanced understanding of rare genetic diseases would take into account the various benefits genetic mistakes confer. This also suggests a cautious approach when editing our own genomes with tools like tools like CRISPR. Even seemingly terrible mutations we would be tempted to eliminate from the genetic pool may confer some secret advantage geneticists have yet to discover.

The study comes at a time when routine genetic testing is the subject of a far-ranging debate. Many doctors fear the release of genetic data to patients would cause undue anxiety. This study didnt support those claims, and goes a distance to undermine the paternalistic style of medicine currently practiced in many developed nations. In the United States, for instance, doctors remain a crucial chokepoint through which patients must pass through to access genetictesting. That said, anumber of direct-to-consumer genetic testing companies like 23andMe are breaking down these barriers, and a host of websites and even smartphone apps exist to help one make sense of their genetic data.

Now read: What is gene therapy?

Read more:
Far More People Than Thought Are Carrying Rare Genetic Diseases - ExtremeTech

Driven by specialised analytics systems and software, big data analytics has decreased the time required to double medical knowledge by half, thus compressing healthcare innovation cycle period, shows the much discussed Mary Meeker study titled Internet Trends 2017.

The presentation of the study isseen as an evidence of the proverbial big data-enabled revolution, that was predicted by experts like McKinsey and Company. "A big data revolution is under way in health care. Over the last decade pharmaceutical companies have been aggregating years of research and development data into medical data bases, while payors and providers have digitised their patient records, the McKinsey report had said four years ago.

Representational image. Reuters

The Mary Meeker study shows that in the 1980s it took seven years to double medical knowledge which has been decreased to only 3.5 years after 2010, on account of massive use of big data analytics in healthcare. Though most of the samples used in the study were US based, the global trends revealed in it are well visible in India too.

"Medicine and underlying biology is now becoming a data-driven science where large amounts of structured and unstructured data relating to biological systems and human health is being generated," says Dr Rohit Gupta of MedGenome, a genomics driven research and diagnostics company based in Bengaluru.

Dr Gupta told Firstpost that big data analytics has made it possible for MedGenome, which focuses on improving global health by decoding genetic information contained in an individual genome, to dive deeper into genetics research.

While any individual's genome information is useful for detecting the known mutations for diseases, underlying new patterns of complicated diseases and their progression requires genomics data from many individuals across populations sometimes several thousands to even few millions amounting to exabytes of information, he said.

All of which would have been a cumbersome process without the latest data analytics tools that big data analytics has brought forth.

The company that started work on building India-specific baseline data to develop more accurate gene-based diagnostic testing kits in the year 2015 now conducts 400 genetic tests across all key disease areas.

What is Big Data

According to Mitali Mukerji, senior principal scientist, Council of Scientific and Industrial Research when a large number of people and institutions digitally record health data either in health apps or in digitised clinics, these information become big data about health. The data acquired from these sources can be analysed to search for patterns or trends enabling a deeper insight into the health conditions for early actionable interventions.

Big data is growing bigger But big data analytics require big data. And proliferation of Information technology in the health sector has enhanced flow of big data exponentially from various sources like dedicated wearable health gadgets like fitness trackers and hospital data base. Big data collection in the health sector has also been made possible because of the proliferation of smartphones and health apps.

The Meeker study shows that the download of health apps have increased worldwide in 2016 to nearly 1,200 million from nearly 1,150 million in the last year and 36 percent of these apps belong to the fitness and 24 percent to the diseases and treatment ones.

Health apps help the users monitor their health. From watching calorie intake to fitness training the apps have every assistance required to maintain one's health. 7 minute workout, a health app with three million users helps one get that flat tummy, lose weight and strengthen the core with 12 different exercises. Fooducate, another app, helps keep track of what one eats. This app not only counts the calories one is consuming, but also shows the user a detailed breakdown of the nutrition present in a packaged food.

For Indian users, there's Healthifyme, which comes with a comprehensive database of more than 20,000 Indian foods. It also offers an on-demand fitness trainer, yoga instructor and dietician. With this app, one can set goals to lose weight and track their food and activity. There are also companies like GOQii, which provide Indian customers with subscription-based health and fitness services on their smartphones using fitness trackers that come free.

Dr Gupta of MedGenome explains that data accumulated in wearable devices can either be sent directly to the healthcare provider for any possible intervention or even predict possible hospitalisation in the next few days.

The Meeker study shows that global shipment of wearable gadgets grew from 26 million in 2014 to 102 million in 2016.

Another area that's shown growth is electronic health records. In the US, electronic health records in office-based physicians in United States have soared from 21 percent in 2004 to 87 percent in 2015. In fact, every hospital with 500 beds (in the US) generate 50 petabytes of health data.

Back home, the Ministry of Electronics and Information Technology, Government of India, runs Aadhar-based Online Registration System, a platform to help patients book appointments in major government hospitals. The portal has the potential to emerge into a source if big data offering insights on diseases, age groups, shortcomings in hospitals and areas to improve. The website claims to have already been used to make 8,77,054 appointments till date in 118 hospitals.

On account of permeation of digital technology in health care, data growth has recorded 48% growth year on year, the Meeker study says. The accumulated mass of data, according to it, has provided deeper insights in health conditions. The study shows drastic increase of citations from 5 million in 1977 to 27 million in 2017. Easy access to big data has ensured that scientists can now direct their investigations following patterns analysed from such information and less time is required to arrive at conclusion.

If a researcher has huge sets of data at his disposal, he/she can also find out patterns and simulate it through machine learning tools, which decreases the time required to arrive at a conclusion. Machine learning methods become more robust when they are fed with results analysed from big data, says Mukerji.

She further adds, These data simulation models, rely on primary information generated from a study to build predictive models that can help assess how human body would respond to a given perturbation, says Mukerji.

The Meeker also study shows that Archimedes data simulation models can conduct clinical trials from data related to 50,000 patients collected over a period of 30 years, in just a span of two months. In absence of this model it took seven years to conduct clinical trials on data related to 2,838 patients collected over a period of seven years.

As per this report in 2016 results of 25,400 number of clinical trial was publically available against 1,900 in 2009.

The study also shows that data simulation models used by laboratories have drastically decreased time required for clinical trials. Due to emergence of big data, rise in number of publically available clinical trials have also increased, it adds.

Big data in scientific research

The developments grown around big-data in healthcare has broken the silos in scientific research. For example, the field of genomics has taken a giant stride in evolving personalised and genetic medicine with the help of big data.

A good example of how big data analytics can help modern medicine is the Human Genome Project and the innumerous researches on genetics, which paved way for personalised medicine, would have been difficult without the democratisation of data, which is another boon of big data analytics. The study shows that in the year 2008 there were only 5 personalised medicines available and it has increased to 132 in the year 2016.

In India, a Bangalore-based integrated biotech company recently launched 'Avestagenome', a project to build a complete genetic, genealogical and medical database of the Parsi community. Avestha Gengraine Technologies (Avesthagen), which launched the project believes that the results from the Parsi genome project could result in disease prediction and accelerate the development of new therapies and diagnostics both within the community as well as outside.

MedGenome has also been working on the same direction. "We collaborate with leading hospitals and research institutions to collect samples with research consent, generate sequencing data in our labs and analyse it along with clinical data to discover new mutations and disease causing perturbations in genes or functional pathways. The resultant disease models and their predictions will become more accurate as and when more data becomes available.

Mukerji says that democratisation of data fuelled by proliferation of technology and big data has also democratised scientific research across geographical boundaries. Since data has been made easily accessible, any laboratory can now proceed with research, says Mukerji.

We only need to ensure that our efforts and resources are put in the right direction, she adds.

Challenges with big data

But Dr Gupta warns that big-data in itself does not guarantee reliability for collecting quality data is a difficult task.

Moreover, he said, In medicine and clinical genomics, domain knowledge often helps and is almost essential to not only understand but also finding ways to effectively use the knowledge derived from the data and bring meaningful insights from it.

Besides, big data gathering is heavily dependent on adaptation of digital health solutions, which further restricts the data to certain age groups. As per the Meeker report, 40 percent of millennial respondents covered in the study owned a wearable. On the other hand 26 percent and 10 percent of the Generation X and baby boomers, respectively, owned wearables.

Similarly, 48 percent millennials, 38 percent Generation X and 23 percent baby boomers go online to find a physician. The report also shows that 10 percent of the people using telemedicine and wearable proved themselves super adopters of the new healthcare technology in 2016 as compared to 2 percent in 2015. Collection of big data.

Every technology brings its own challenges, with big data analytics secure storage and collection of data without violating the privacy of research subjects, is an added challenge. Something, even the Meeker study does not answer.

Digital world is really scary, says Mukerji.

Though we try to secure our data with passwords in our devices, but someone somewhere has always access to it, she says.

The health apps which are downloaded in mobile phones often become the source of big-data not only for the company that has produced it but also to the other agencies which are hunting for data in the internet. "We often click various options while browsing internet and thus knowingly or unknowingly give a third party access to some data stored in the device or in the health app, she adds.

Dimiter V Dimitrov a health expert makes similar assertions in his report, 'Medical Internet of Things and Big Data in Healthcare'. He reports that even wearables often have a server which they interact to in a different language providing it with required information.

Although many devices now have sensors to collect data, they often talk with the server in their own language, he said in his report.

Even though the industry is still at a nascent stage, and privacy remains a concern, Mukerji says that agencies possessing health data can certainly share them with laboratories without disclosing patient identity.

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Big data analytics in healthcare: Fuelled by wearables and apps, medical research takes giant leap forward - Firstpost

Precision medicine is hot and Konica Minolta wants a piece of the action. To that end, its Healthcare Americas arm is paying $1 billion to acquire Ambry Genetics.

Innovation Network Corporation of Japan (INCJ) is helping to fund the deal.Konica Minolta Healthcare Americas and INCJwill make an all-cash payment of $800 million. Ambry shareholders will get up to $200 million over the next two years.

Konica views the deal as a stepping stone marking its debut as a player in the space and plans to bring Ambrys products to Japan and then to Europe, according to a news release. Shoei Yamana, Konica Minolta CEO said in a news release that the deal marks the first in a series of initiatives to build Konicas precision medicine profile.

The future of medicine is patient-focused. Together with Ambry, we will have the most comprehensive set of diagnostic technologies for mapping an individuals genetic and biochemical makeup, as well as the capabilities to translate that knowledge into information the medical community can use to discover, prevent, and cost-effectively treat diseases, Yamana said. This will not only serve as the future foundation for our healthcare business but will pave the way for a fundamental shift in the way medicine is practiced globally.

Ambrys diagnostic offerings span multiple fields, including neurology, oncology and womens health. As with most genomics services, the business will also be generating rich data as a byproduct of its sales. Konica may be able to tap into this information in myriad ways, from drug discovery to companion diagnostics and more. Its the foundations of todays precision medicine work.

Photo: maxsattana, Getty Images

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Konica Minolta establishing itself as precision medicine player with $1B Ambry Genetics deal - MedCity News

BBC News

6.8m genetic medicine plan for targeted treatment - BBC News BBC News Patients in Wales will benefit from stronger services and more expertise in genetic medicine, under a new strategy. The 6.8m plan has been designed to ensure ... Tories ask for government assurances over genetic medicine pledge ...Barry and District News Government strategy strives for tailor-made healthcarePenarth Times all 4 news articles »

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6.8m genetic medicine plan for targeted treatment - BBC News - BBC News

July 5, 2017 Credit: Cancer Research UK

Cancer patients should have routine access to genetic testing to improve diagnosis and treatment, according to England's chief medical officer.

Despite the UK being a world leader in genomic medicine its full potential is still not being realised, Professor Dame Sally Davies said in a new report.

Davies urged clinicians and the Government to work together and make wider use of new genetic techniques in an attempt to improve cancer survival rates.

Genetic testing can pinpoint the faults in DNA that have led to a cancer forming. Different cancers have different faults, and these determine which treatments may or may not work.

Such testing could lead to patients being diagnosed faster and receiving more targeted or precise treatments.

Davies said that "the age of precision medicine is now" and that the NHS must act quickly to remain world class.

"This technology has the potential to change medicine forever but we need all NHS staff, patients and the public to recognise and embrace its huge potential." said Davies.

Sir Harpal Kumar, Cancer Research UK's chief executive, agreed, saying that it would be a disservice to patients if the UK were slow to respond to innovations in this area.

The report recommends that within 5 years training should be available to current and future clinicians and that all patients should be being offered genomic tests just as readily as they're given MRI scans today.

Davies also called for research and international collaboration to be prioritised, along with investment in research and services so that patients across the country have equal access.

However the report recognises potential challenges such as data protection issues and attitudes of clinicians and the public.

"This timely report from the chief medical officer showcases just how much is now possible in genomics research and care within the NHS," added Sir Kumar.

"Cancer Research UK is determined to streamline research, to find the right clinical trial for cancer patients and to ensure laboratory discoveries benefit patients".

And the design of clinical trials are starting to change. A number of trials are underway, like Cancer Research UK's National Lung Matrix Trial with AstraZeneca and Pfizer, where patients with a certain type of lung cancer are assigned a specific treatment based on the genetic makeup of their cancer.

However, Sir Harpal Kumar stressed that to bring the report's vision to life the Government, the NHS, regulators and research funders need to act together.

Explore further: Adding abiraterone to standard treatment improves prostate cancer survival by 40 percent

Cancer Research UK is partnering with pharmaceutical companies AstraZeneca and Pfizer to create a pioneering clinical trial for patients with advanced lung cancer marking a new era of research into personalised medicines ...

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Greater access to genetic testing needed for cancer diagnosis and ... - Medical Xpress

July 5, 2017 Credit: CC0 Public Domain

Pioneering research using the tropical zebrafish could provide new insights into the genetic basis of myopathy, a type of human muscle disease.

An international research team, led by Professor Philip Ingham FRS, inaugural Director of the University of Exeter's Living Systems Institutehas taken the first steps in determining the central role a specific gene mutation in a poorly characterised human myopathy.

Myopathies are diseases that prevent muscle fibres from functioning properly, causing muscular weakness. At present, there is no single treatment for the disease, as it can develop via a number of different pathways.

One particular type is nemaline myopathy, which primarily affects skeletal muscles and can lead to sufferers experiencing severe feeding and swallowing difficulties as well as limited locomotor activity.

Mutations in a specific gene, called MY018B, have recently been found to be present in people exhibiting symptoms of this disease, but the role these mutations play in muscle fibre integrity has until now been unclear.

In this new research, the Ingham team, based in Singapore and Exeter, has used high-resolution genetic analysis to create a zebrafish model of MYO18B malfunction; this research takes advantage of the remarkable similarity between the genomes of zebrafish and humans,which have more than 70 per cent of their genes in common.

The Singapore/Exeter team found that the MYO18B gene is active specifically in the 'fast-twitch' skeletal muscles of the zebrafish, typically used for powerful bursts of movement. Crucially, by studying fish in which the MYO18B gene is disrupted, they were able to show that it plays an essential role in the assembly of the bundles of actin and myosin filaments that give muscle fibres their contractile properties.

The team believe this new research offers a vital new step towards understanding the cause of myopathy in humans, which in turn could give rise to new, tailored treatments in the future.

The leading research is published in the scientific journal, Genetics.

Professor Ingham, said: "The identification of a MYO18B mutation in zebrafish provides the first direct evidence for its role in human myopathy and gives us a model in which to study the molecular basis of MYO18B function in muscle fibre integrity."

A pioneer in the genetic analysis of development using fruit flies and zebrafish as model systems, Prof Ingham is internationally renowned for his contributions to several influential discoveries in the field of developmental biology over the last century.

This is the latest research by Professor Ingham that has revealed important links between the processes that underpin normal embryonic development and disease.

His co-discovery of the 'Sonic Hedgehog' gene, recognised as one of 24 centennial milestones in the field of developmental biology by Nature, in 2004, led directly to the establishment of a biotechnology company that helped develop the first drug to target non-melanoma skin cancer.

The research comes at the University of Exeter holds the official opening of the Living Systems Institute with an Opening Symposium event, from July 5-6 2017.

Two Nobel Laureates, Sir Paul Nurse FRS and Christiane Nsslein-Volhard ForMemRS, who separately won the Nobel Prize for Physiology or Medicine, will deliver keynote speeches as part of the opening event.

The high-profile event, held at the University's Streatham Campus marks the official opening of the LSIa 52 million inter-disciplinary research facility designed to bring new, crucial insights into the causes and preventions of some of the most serious diseases facing humanity.

A Zebrafish Model for a Human Myopathy Associated with Mutation of the Unconventional Myosin MYO18B is published in Genetics.

Explore further: Zebrafish help identify mutant gene in rare muscle disease

Journal reference: Genetics

Provided by: University of Exeter

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Research could give insight into genetic basis of of the human muscle disease, myopathy - Medical Xpress

BBC News

Chief medical officer calls for gene testing revolution - BBC News BBC News Cancer patients should be routinely offered DNA tests to help select the best treatments for them, according to England's chief medical officer. Prof Dame Sally ... UK medical chief vows to spread 'genetics dream'Financial Times All cancer patients should have their DNA tested to save lives, Chief Medical Officer saysTelegraph.co.uk Cancer breakthrough: Treatment could be personalised to YOU by using your genesExpress.co.uk Sky News -iNews -BT.com all 25 news articles »

Continued here:
Chief medical officer calls for gene testing revolution - BBC News - BBC News

Cancer patients should have routine access to genetic testing to improve diagnosis and treatment, according to Englands chief medical officer.

Despite the UK being a world leader in genomic medicine its full potential is still not being realised, Professor Dame Sally Davies said in a new report.

This timely report from the chief medical officer showcases just how much is now possible in genomics research and care within the NHS. - Sir Harpal Kumar, Cancer Research UK

Davies urged clinicians and the Government to work together and make wider use of new genetic techniques in an attempt to improve cancer survival rates.

Genetic testing can pinpoint the faults in DNA that have led to a cancer forming. Different cancers have different faults, and these determine which treatments may or may not work.

Such testing could lead to patients being diagnosed faster and receiving more targeted or precise treatments.

Davies said that the age of precision medicine is now and that the NHS must act quickly to remain world class.

This technology has the potential to change medicine forever but we need all NHS staff, patients and the public to recognise and embrace its huge potential. said Davies.

Sir Harpal Kumar, Cancer Research UKs chief executive, agreed, saying that it would be a disservice to patients if the UK were slow to respond to innovations in this area.

The report recommends that within 5 years training should be available to current and future clinicians and that all patients should be being offered genomic tests just as readily as theyre given MRI scans today.

Davies also called for research and international collaboration to be prioritised, along with investment in research and services so that patients across the country have equal access.

However the report recognises potential challenges such as data protection issues and attitudes of clinicians and the public.

This timely report from the chief medical officer showcases just how much is now possible in genomics research and care within the NHS, added Sir Kumar.

Cancer Research UK is determined to streamline research, to find the right clinical trial for cancer patients and to ensure laboratory discoveries benefit patients.

And the design of clinical trials are starting to change. A number of trials are underway, like Cancer Research UKs National Lung Matrix Trial with AstraZeneca and Pfizer, where patients with a certain type of lung cancer are assigned a specific treatment based on the genetic makeup of their cancer.

However, Sir Harpal Kumar stressed that to bring the reports vision to life the Government, the NHS, regulators and research funders need to act together.

View original post here:
Greater access to genetic testing needed for cancer diagnosis and treatment - Cancer Research UK

Two new studies suggest that one in five seemingly healthy people hasDNA mutations that puts him or herat increased risk for genetic disease.

BlackJack3D/iStockPhoto

By Ryan CrossJun. 26, 2017 , 6:15 PM

Some doctors dream of diagnosing diseasesor at least predicting disease riskwith a simple DNA scan. But others have said the practice, which could soon be the foundation of preventative medicine, isnt worth the economic or emotional cost. Now, a new pair of studies puts numbers to the debate, and one is the first ever randomized clinical trial evaluating whole genome sequencing in healthy people. Together, they suggest that sequencing the genomes of otherwise healthy adults can for about one in five people turn up risk markers for rare diseases or genetic mutations associated with cancers.

What that means for those people and any health care system considering genome screening remains uncertain, but some watching for these studies welcomed the results nonetheless. It's terrific that we are studying implementation of this new technology rather than ringing our hands and fretting about it without evidence, says Barbara Biesecker, a social and behavioral researcher at the National Human Genome Research Institute in Bethesda, Maryland.

The first genome screening study looked at 100 healthy adults who initially reported their family history to their own primary care physician. Then half were randomly assigned to undergo an additional full genomic workup, which cost about $5000 each and examined some 5 million subtle DNA sequence changes, known as single-nucleotide variants, across 4600 genessuch genome screening goes far beyond that currently recommended by the American College of Medical Genetics and Genomics (ACMG), which suggests informing people of results forjust 59 genes known or strongly expected to cause disease.

Of the 50 participants whose genomes were sequenced, 11 had alterations in at least one letter of DNA suspected to causeusually rarediseases, researchers report today in The Annals of Internal Medicine. But only two exhibited clear symptoms. One was a patient with extreme sensitivity to the sun. Their DNA revealed a skin condition called variegate porphyria. Now that patient knows they will be much less likely to get bad sunburns or rashes if they avoid the sun and certain medications, says Jason Vassy, a primary care clinician-investigator at Veteran Affairs Boston Healthcare System and lead author of the study.

The team also found that every sequenced patient carried at least one recessive mutation linked to a diseasea single copy of a mutant gene that could cause an illness if two copies are present. That knowledge can be used to make reproductive decisionsa partner may get tested to see if they have a matching mutationand prompt family members to test themselves for carrier status. And in what Vassy calls a slightly more controversial result, the team examined participants chances of developing eight polygenic diseases, conditions that are rarely attributed to a single genetic mutation. Here, they compiled the collective effects of multiple genesup to 70 for type II diabetes and 60 for coronary heart diseaseto predict a patients relative risk of developing the disease.

Just 16% of study volunteers who only reported their family history were referred to genetic counselors or got follow-up laboratory tests. In the genome sequencing group, the number was 34%.

Some researchers have expressed concern that such whole genome screening will skyrocket medical costs or cause undue psychological harm. Aside from the initial cost of sequencing (which was covered by the study), patients who underwent the genomic screen paid an average of $350 additional in healthcare costs over the next 6 months, Vassy and colleagues reported. But contrary to fears of emotional trauma, neither the sequencing group nor the control group showed any changes in anxiety or depression 6 months after the study.

Vassy stresses that their study was small and needs follow-up, but it still impressed Christa Martin, a geneticist at Geisinger Health System, in Danville, Pennsylvania, who worked on the ACMGs recommendations for genome sequencing. I almost feel like the authors undersold themselves, she says. Many of their patients are making health behavioral changes, so they are using the information in a positive way.

The study was extremely well designed and very appropriately run, adds Barbara Koenig, a medical anthropologist who directs the University of CaliforniaSan Francisco Bioethics Program. But she still questions the assumption by many physicians, ethicists, and patient advocates that more information is always beneficial. It is just hard to know how all this information is going to be brought together in our pretty dysfunctional healthcare system.

Another paper published last week on the preprint server bioRxiv, which has not yet undergone peer review, yields similar results. Using whole-exome sequencing, which looks only at the protein-coding regions of the genome, Michael Snyder, director of the Stanford Center for Genomics and Personalized Medicine in Palo Alto, California, and colleagues found that 12 out of 70 healthy adults, or 17%, unknowingly had one or more DNA mutations that increased the risk for genetic diseases for which there are treatment or preventative options.

Both studies suggest that physicians should look at genes beyond the ACMGs 59 top priorities, Snyder says. He argues that whole-genome sequencing should be automatically incorporated into primary care. You may have some super-worriers, but I would argue that the information is still useful for a physician to have. Vassy, however, says that there isnt yet enough evidence to ask insurance companies to reimburse whole genome sequencing of healthy patients.

We like a quick fix and the gene is an important cultural icon right now, so we probably give it more power than it really has, Koenig says. But these are still really early days for these technologies to be useful in the clinic.

See the article here:
One in five 'healthy' adults may carry disease-related genetic mutations - Science Magazine

June 30, 2017

Uncovering rare susceptibility variants that contribute to the causes of complex diseases requires large sample sizes and massively parallel sequencing technologies. These sample sizes, often made up of exome and genome data from tens to hundreds of thousands of individuals, are often too large for current analytical tools to process. A team at Baylor College of Medicine, led by Dr. Suzanne Leal, professor of molecular and human genetics, has developed new software called SEQSpark to overcome this processing obstacle. A study on the new technology appears in The American Journal of Human Genetics.

"To handle these large data sets, we built the SEQSpark tool based on the commonly used Spark program, which allows SEQSpark to utilize multiple processing platforms to increase the speed and efficiency of performing data quality control, annotation and rare variant association analysis," Leal said.

To test and validate the versatility and speed of SEQSpark, Leal and her team analyzed benchmarks from the whole genome sequence data from the UK10K, testing specifically for waist-to-hip ratios.

"The analysis and related tasks took about one and a half hours to complete, in total. This includes loading the data, annotation, principal components analysis and single and rare variant aggregate association analysis for the more than 9 million variants present in this sample set," explained Di Zhang, a postdoctoral associate in the Leal lab at Baylor and first author on the paper.

To evaluate SEQSpark's performance in a larger data set, Leal and the research team generated 50,000 simulated exomes. The SEQSprak program ran the analysis for a quantitative trait using several variant aggregate association methods in an hour and forty-five minutes.

When compared to other variant association tools, SEQSpark was consistently faster, reducing computation to a hundredth of the time in some cases.

"What is unique about SEQSpark is that it is scalable, and smaller labs can run it without super specific hardware, and it can also be run in a multi-server environment to increase its speed and capacity for large genetic data sets," Zhang said. "It is ideal for large-scale genetic epidemiological studies and is highly efficient from a computational standpoint."

"We see this software as being very useful as the demand for the analysis of massively parallel sequence data grows. SEQSpark is highly versatile, and as we analyze increasingly large sets of rare variant data, it has the potential to play a key role in furthering personalized medicine," Leal said.

In the future, Leal and her team will continue to test and increase SEQSpark's capabilities and will be analyzing soon data sets that have 500,000 samples or more.

Explore further: Genetic test for familial data improves detection genes causing complex diseases such as Alzheimer's

More information: Di Zhang et al. SEQSpark: A Complete Analysis Tool for Large-Scale Rare Variant Association Studies using Whole-Genome and Exome Sequence Data, The American Journal of Human Genetics (2017). DOI: 10.1016/j.ajhg.2017.05.017

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