Category Archives: Gene Medicine

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease, according to scientists at the University of Washington (UW) Medicine Institute for Stem Cell and Regenerative Medicine.

The disease arises from a mutation in genes that normally make myotubularin, a protein essential for proper muscle function. Puppies with this naturally occurring mutation exhibit several features of babies with the same defective gene. The rare disorder, called X-linked myotubular myopathy, or XLMTM, affects only males. It causes fatal muscle wasting. Both dogs and boys with the disease typically succumb in early life due to breathing difficulties.

For decades, researchers have struggled to find suitable treatments for genetic muscle diseases like this one. Collaborating research groups in the United States and France found a way to safely replace the disease-causing MTM gene with a healthy gene throughout the entire musculature of affected dogs.

Their most recent findings ("Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs") werepublished online inMolecular Therapy.The paper reports that diseased dogs treated with a single infusion of the corrective therapy were indistinguishable from normal animals 1 year later.

"This regenerative technology allowed dogs that otherwise would have perished to complete restoration of normal health," said Martin K. "Casey" Childers, Ph.D., UW medicine researcher and physician. Dr. Childers is a professor of rehabilitation medicine at the University of Washington School of Medicine and co-director of the Institute for Stem Cell and Regenerative Medicine.

Gene therapy holds the promise to treat many inherited diseases. To date, this approach has not been widely translated into treatment of skeletal muscle disorders.

"We report here a gene therapy dose-finding study in a large animal model of a severe muscle disease where a single treatment resulted in dramatic rescue," said Dr. Childers. The findings demonstrate potential application across a wide range of diseases and broadly translate to human studies. The data supports the development of gene therapy clinical trials for myotubular myopathy, the researchers concluded.

The study was conducted in collaboration with Harvard University, Medical College of Wisconsin, Virginia Tech, INSERM, and Genethon.

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Rare Muscle Disease Treated Successfully with Gene Therapy - Genetic Engineering & Biotechnology News

February 16, 2017 Credit: UNIGE

When a child is conceived, he or she receives DNA from both parents. The child's own genome thus consists of a maternal and a paternal genome. However, some genesabout 100 out of the 20,000 encoded genes are exclusively expressed either from the maternal or from the paternal genome, with the other copy of the gene remaining silent. We know that these imprinted genes are more likely to lead to serious genetic diseases, such as PraderWilli or Angelman syndrome. Researchers at the University of Geneva (UNIGE), Switzerland, have devised a new technique, based on a combination of biology and bioinformatics, to quickly and accurately detect the imprinted genes expressed in each of the cell types that constitute the human organs. This major breakthrough will improve our understanding and diagnosis of genetic diseases. The study can be read in full in the American Journal of Human Genetics.

The research team, led by Professor Stylianos Antonarakis from the Department of Genetic Medicine and Development in the Faculty of Medicine at UNIGE, focused on genomic imprinting. This is a set of genes exclusively expressed from the genetic code inherited either from the father (the paternal allele) or from the mother (maternal allele). Why is there so much interest in the identification of the imprinted genes? Because if a deleterious mutation affects the functional allele, it cannot be compensated by the expression of the second silent allele, likely causing a serious genetic disease. The goal, therefore, is to determine the imprinted genes in all cell types of human body tissues that are liable to cause these kind of diseases.

Until recently, millions of cells were analysed together without distinction. "We have now developed a new technique with a better resolution, known as Human Single-Cell Allele-Specific Gene Expression," explains Christelle Borel, UNIGE researcher. "The process can be used to simultaneously examine the expression of the two alleles, paternal and maternal, of all known genes in each individual cell. The method is fast and can be carried out on thousands of single cells with the utmost precision using next-generation sequencing technology." The heterogeneity of each tissue of the body is thus analysed in detail while searching for imprinted genes in disease-relevant tissue. The individual's genome is sequenced, as is the genome of both parents, in order to identify the parental origin of the alleles transcribed in the person's single cell.

Each cell is unique

Federico Santoni, first author of the study and researcher at UNIGE and HUG (Geneva University Hospitals) further explains, "We establish the profile of the allelic expression for thousands of genes in each single cell. We then process this data with a novel computational and statistical framework to identify the specific signature of each imprinted gene, enabling us to accurately record them." This new technique redefines the landscape of imprinted genes by examining all cell types, and can be applied to all tissues affected by diseases, such as cardiac and brain tissue. Moreover, the scientists have discovered novel imprinted genes and demonstrated that some were restricted to certain tissues or cell types.

This technique focuses on the specific characteristics of each individual by treating each cell as a single entity. This concept, called Single-cell Genomics, is part of an emerging field that is assuming an all-important role at UNIGE, which sees it as the future of medicine that will be personalised rather than generalised. Thanks to the technique pioneered by UNIGE researchers, it will be possible to identify new disease causing genes and to adapt a specific and targeted treatment for individual patients.

Explore further: Expanding the brain: Research identifies more than 40 new imprinted genes

More information: Federico A. Santoni et al. Detection of Imprinted Genes by Single-Cell Allele-Specific Gene Expression, The American Journal of Human Genetics (2017). DOI: 10.1016/j.ajhg.2017.01.028

It's among the cornerstones of biology: All mammals inherit two copies one from their mother, the other from their fatherof every gene, in part to act as a backstop against genetic problems. If a gene is damaged or ...

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Researchers at Karolinska Institutet and Ludwig Institute for Cancer Research have characterized how and to what degree our cells utilize the gene copies inherited from our mother and father differently. At a basic level ...

The development of the cerebral cortex played a major role in the evolution of mankind. Scientists are now studying the emergence of its cellular microstructure with high resolution methods. Neuroscientists at the University ...

Personalized medicine, which involves tailoring health care to each person's unique genetic makeup, has the potential to transform how we diagnose, prevent and treat disease. After all, no two people are alike. Mapping a ...

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease. UW Medicine Institute for Stem Cell and Regenerative ...

A genomic study of baldness identified more than 200 genetic regions involved in this common but potentially embarrassing condition. These genetic variants could be used to predict a man's chance of severe hair loss. The ...

Purdue University and Indiana University School of Medicine scientists were able to force an epigenetic reaction that turns on and off a gene known to determine the fate of the neural stem cells, a finding that could lead ...

Just before Rare Disease Day 2017, a study from the Monell Center and collaborating institutions provides new insight into the causes of trimethylaminura (TMAU), a genetically-transmitted metabolic disorder that leads to ...

Monash University and Danish researchers have discovered a gene in worms that could help break the cycle of overeating and under-exercising that can lead to obesity.

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Stepping up the hunt for genetic diseases - Medical Xpress

February 16, 2017 by Merlin Crossley, The Conversation Gene therapy is growing in its capabilities, but there should be limits to its use. Credit: Shutterstock

If you recognise the words "CRISPR-mediated gene editing", then you'll know that our ability to alter DNA has recently become much more efficient, faster and cheaper.

This has inevitably led to serious discussions about gene therapy, which is the direct modification of someone's DNA to rectify a genetic disorder, such as sickle cell anaemia or haemophilia. And you may also have heard of deliberate genetic enhancement, to realise a healthy person's dreams of improving their genome.

Both of these issues have now been tackled in a comprehensive report on gene editing released today by the US National Academy of Science and National Academy of Medicine.

The message is fairly simple: relax, we've seen this all before, little if any harm has eventuated, and society is well placed to move forward together on this.

A definite maybe

Of all human technologies, recombinant DNA has arguably been one of the safest. There have been multiple benefits in both medicine and agriculture. And the legitimate concerns that arose when viruses were first mixed with bacterial genes, when cloning was first introduced, and when stem cells were developed, have not come to pass.

I cannot list all the benefits here, but if you have received the Hepatitis B vaccine or Australian Ian Fraser's Gardasil vaccine, which protects against cervical cancer viruses, you have been protected from disease thanks to recombinant DNA technology.

However, you probably haven't received somatic gene therapy, which is gene alteration directed at fixing one cell type, such as defective blood or liver cells. This is because this therapy only touches a tiny number of people, probably fewer than 1,000 worldwide, and again the benefits have outweighed the risks.

But there is one new message in the report that will grab the headlines.

That is the view on human germline gene therapy, which entails modifications that would be passed on to children and then to their children. This kind of gene therapy has been considered highly controversial. But this time, instead of a simple no thanks there's a definite maybe, provided the therapy is targeted at a severe disease as a last resort.

There will be alarm in some circles at the very mention of germline gene therapy, although perhaps not from the very few people who might be contemplating such treatment for the sake of their future children.

The authors of the report, who are among the mostly highly respected experts in the world, are well aware that many people will not be comfortable with the thought of germline gene therapy. They stress the need for extensive consultation, the meeting of strict criteria, and close regulation.

But in weighing up safety and efficacy, social and individual benefit, they clearly don't want to see a reflex ban put in place that may limit options if this technology can be used to make the life of some individuals better.

On one hand, they are right. This technology is not a threat to the fabric of society. Nor, I'd say, is this a genie that could not be put back in the bottle; gene editing could be reversed.

Nor, like the Sorcerer's Apprentice's broomsticks, will it multiply and spread when we try to restrain it. This is not like letting slip a virus, cane toads, oozing radioactive waste or carbon emissions into the atmosphere.

Seeking germline gene therapy in order to have a disease-free child would be a choice made at a personal level and those not wishing to participate should never feel compelled to do so.

Except, of course, the children who would not have a say in it. But also for them the risks might well outweigh the benefits. And, one way or another, parents already make life-determining choices for their children and sometimes for their children's children.

Even those seeking germline therapy for the sake of their children would mostly have alternatives, such as preimplantation diagnosis, which itself also has ethical considerations. There are no easy answers here.

So I can understand the report's conclusion, although I also believe there are risks, which I'll mention below.

Hard to abuse

There are other aspects of the report worth mentioning. It confirms that we already do properly regulate laboratory-based gene modifications, and we have learned so much from previous somatic gene therapy efforts that we are well placed to push on safely with both research and somatic treatments. I agree with this.

It also says that actual genetic enhancements should be avoided. There is evidence that society is uncomfortable with the idea of individuals, who are not suffering from disease, improving either themselves through somatic therapy or their bloodlines through germline genetic enhancement.

Some people might want more copies of the p53 tumour suppressing gene or to lose their CCR5 gene, which helps HIV invade cells, in order to give their children possible protection from cancer or HIV respectively, but I'd have to say it isn't worth the risk.

I would add that, ethical reservations aside, the sheer complexity of our genomes, and the rather involved and lengthy process of human reproduction, means that I have no concerns that even the craziest world leader could ever generate an army of super-mutants. Such an ambition would be defeated by not knowing which genes to alter, not to mention the requirement to assemble tens of thousands of surrogate mothers, then wait 20 years for the army to mature.

Yes, it is possible that someone somewhere will attempt germline gene enhancement as a stunt. That would be wrong and dangerous, and a risk for the child. But it would not threaten society any more deeply than many other obscene and regrettable individual crimes that sadly occur every day.

Germline gene therapy is illegal in many countries, and although there is a risk that unfortunate "medical tourism" may occur at some stage, I don't expect this to be a greater problem than the already widespread snake-oil selling that is a feature of many economies.

No emergency

So am I comfortable with this report and confident that it covers the ethical issues? I think it is superbly written. It is accurate, up to date, balanced, thoughtful, and covers experiments, somatic therapy, germline therapy, genetic enhancement, societal responses, and the need for public consultation and careful regulation. There is no emergency here.

My main concern is that raising the prospect of germline gene therapy will trigger discussions that will divert us from more pressing issues.

I do worry that introducing this apex concept as a possibility may increase the number of people who fixate on what gene therapy could deliver and thus may be lured into medical tourism, both desperate patients and also foolish investors, and all the while charlatans will profit from peddling promise.

I worry that raising hopes too high too quickly will ultimately cause a backlash against more moderate science.

I also worry that even conventional funding bodies will succumb to understandable pressures to fund translational research prematurely and this will actually waste large amounts of valuable public money.

And I worry about a hysterical reaction that could divide society along political lines with people lining up for or against germline gene therapy based on their political positions or personal beliefs rather than a sober examination of the facts, risks and contexts.

Finally, I worry that the focus on human modification will distract us from other issues, such as the use of CRISPR-mediated gene drives that could be used to eradicate rapidly reproducing organisms such as mosquitoes, and could thus be used for both great good or great harm.

But I don't feel the burden of worry too much because I know that, as a scientist, I can and should share the weight of my concerns with society.

Explore further: With stringent oversight, heritable human genome editing could be allowed: report

This article was originally published on The Conversation. Read the original article.

Clinical trials for genome editing of the human germline - adding, removing, or replacing DNA base pairs in gametes or early embryos - could be permitted in the future, but only for serious conditions under stringent oversight, ...

Recent evidence demonstrating the feasibility of using novel CRISPR/Cas9 gene editing technology to make targeted changes in the DNA of human embryos is forcing researchers, clinicians, and ethicists to revisit the highly ...

The National Academy of Sciences and National Academy of Medicine issued a 258-page report Tuesday (Feb. 14) focused on human genome editing. It lays out principles and recommendations for the U.S. government and governments ...

At the conclusion of the recent International Summit on Human Gene Editing in Washington, DC, its organizing committee released a much-anticipated statement recommending how human genetic engineering should be regulated. ...

Don't expect designer babies any time soonbut a major new ethics report leaves open the possibility of one day altering human heredity to fight genetic diseases, with stringent oversight, using new tools that precisely ...

Personalized medicine, which involves tailoring health care to each person's unique genetic makeup, has the potential to transform how we diagnose, prevent and treat disease. After all, no two people are alike. Mapping a ...

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease. UW Medicine Institute for Stem Cell and Regenerative ...

A genomic study of baldness identified more than 200 genetic regions involved in this common but potentially embarrassing condition. These genetic variants could be used to predict a man's chance of severe hair loss. The ...

Purdue University and Indiana University School of Medicine scientists were able to force an epigenetic reaction that turns on and off a gene known to determine the fate of the neural stem cells, a finding that could lead ...

Just before Rare Disease Day 2017, a study from the Monell Center and collaborating institutions provides new insight into the causes of trimethylaminura (TMAU), a genetically-transmitted metabolic disorder that leads to ...

Monash University and Danish researchers have discovered a gene in worms that could help break the cycle of overeating and under-exercising that can lead to obesity.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

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Human genome editing report strikes the right balance between risks and benefits - Medical Xpress

Metro

Cancer could be wiped off the face of the earth with new gene editing techniques Metro Then the cell's own DNA repair machinery can be exploited to insert the 'pasted' genetic material. Dr Westra said: 'Gene editing .. is causing a true revolution in science and medicine, because it allows for very precise DNA surgery. 'A mutation in a ... Gene editing could bring an end to all inherited disease and cancer, expert saysThe Independent All inherited diseases could be cured within 20 years thanks to gene editing breakthroughMirror.co.uk all 3 news articles »

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Cancer could be wiped off the face of the earth with new gene editing techniques - Metro

Scientists should be allowed to altera persons DNA in ways that will be passed on to future generations, but only to prevent serious and strongly heritable diseases, according to a new report from the National Academy of Sciences and the National Academy of Medicine.

However, tinkering with these genes in orderto enhance or alter traits such as strength, intelligence or beauty should remain off-limits, the report authors concluded.

Changing theso-called germline effectively, editing humanitys future by altering genes in human reproductive cells is illegal in the United States. It has largely been considered ethically off-limits here as well, at least whilebioethicists and scientists pondered the unforeseen effects and unexamined moral dilemmas of using new gene-editing technologies.

However, scientists have moved forward aggressively to explore the feasibility of altering disease genes in other adult human cells with a revolutionarytechnique known asCRISPR-Cas9. It is widely believed that gene editing of this sort could treat patients with metabolic disorders, certain cancers, anda range of otherdiseases that arise from genetic mutationswithout altering the germline.

Last year, Chinese scientists launched a trial that uses CRISPR-Cas9 in a treatment for lung cancer. While the trials outcome is awaited with high anticipation, scientists outside of China have expressed concern that ethical reservations in the United States and Europe will put themat a disadvantage.

CRISPR-Cas9 makesgene editing more straightforward, more precise and far more widespread. As such, the National Academies report acknowledgesthat changingheritable DNA ineggs, sperm and early embryosis fast becoming a realistic possibility that deserves serious consideration.

The 22-memberpanel of scientists and bioethicists who produced the report completed a comprehensive review of the issues raised by that prospect.

Clinical trials involving germline editing should onlybe pursuedto treat diseases that cannot be improvedwith reasonable alternatives, the committee said. In addition, they added,scientists should convincingly demonstratethey are targeting a gene that eithercauses or strongly predisposes a carrier to a serious disease or condition, and that they have weighed the likely risks and benefits of altering that gene.

These clinical trials should be conducted under public scrutiny that takes into account issues ofsocietal fairness, personal dignityand scientific integrity, the panel said.

Finally, scientists should conduct long-term follow-up studies to discern how gene editing affects subsequent generations.Public debate and discussion about the technologyshould continue, the panel added.

Genome editing research is very much an international endeavor, and all nations should ensure that any potential clinical applications reflect societal values and be subject to appropriate oversight and regulation, saidMIT cancer researcher Richard O.Hynes, who co-chaired the panel with University of Wisconsin-Madison bioethicist R. Alta Charo. These overarching principles and the responsibilities that flow from them should be reflected in each nations scientific community and regulatory processes.

Dr. J. Patrick Whelan, an immunologist and bioethicist who was not on the panel, said the grouphas asked the compelling questions, sparkinga conversation that must keep up with a rapid pace of scientific discovery in this field. He called the reportsrelease a fantastic development.

What theyre saying is, lets start the conversation, maintain ethical structures along the way, and hopefully do this the right way, said Whelan, who serves on the advisory board of USCs Institute for Advanced Catholic Studies.

The international panel included members from the U.S., China, France, Israel andItaly.Their report was underwritten in part by the Department of Defenses Advanced Research Projects Agency and the U.S. Food and Drug Administration.

melissa.healy@latimes.com

Follow me on Twitter @LATMelissaHealy and "like" Los Angeles Times Science & Health on Facebook.

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To prevent serious medical conditions, scientists should be able to edit people's DNA, panel says - Los Angeles Times

The Atlantic

Harvard and MIT Scientists Win Gene-Editing Patent Fight New York Times The Broad Institute in Cambridge, Mass., will retain potentially lucrative rights to a powerful gene-editing technique that could lead to major advances in medicine and agriculture, the federal Patent and Trademark Office ruled on Wednesday. The ... What the CRISPR Patent Decision Means for Gene EditingThe Atlantic Broad Institute wins case over gene-editing patents, boosting Editas sharesBoston Business Journal Broad Institute Wins Big Battle Over CRISPR Gene-Editing PatentNPR 24/7 Wall St. -Motley Fool -Lexington Herald Leader all 52 news articles »

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Harvard and MIT Scientists Win Gene-Editing Patent Fight - New York Times

Editing of human cells to alter traits handed down to future generations may one day be ethically permissible, said a committee co-chaired by bioethicist Alta Charo, a professor at the University of Wisconsin School of Law.

"It is not ready now, but it might be safe enough to try in the future," Charo told National Public Radio. "And if certain conditions are met, it might be permissible to try it."

Charo, along with UW-Madison science communication professor Dietram Scheufele, was part of a committee appointed by the National Academies of Sciences and Medicine that on Tuesday released a groundbreaking report on the ethics of human gene editing.

Dietram Scheufele

Despite the consensus at a 2015 international summit in Washington, D.C., where scientists concluded they should not perform gene editing on reproductive cells intended for establishing a pregnancy, the new report advises that such research might be permitted after further work to develop appropriate risk/benefit standards.

The panel recommended alteration of genes in human reproductive cells, sometimes called germ lines, be allowed only to prevent serious disease or disability for which there is no treatment. On the other hand, the potential benefits of human germ line editing to enhance desired inherited traits like beauty, intelligence or strength are at this time unlikely to outweigh risks like the inheritance of undesired mutations, panel members found.

Up until now, weve been talking only hypothetically and most people assumed we simply wouldnt ever do this, Charo told Nature. We are not saying that you have to or you should, but we are saying that if you can meet these criteria it is permissible.

In the United States, the use of federal funds for research involving the creation of a human embryo to include an inheritable modification is prohibited. But the committee defined a set of criteria for use in other countries, or in the U.S. if restrictions were allowed to expire. The criteria include: absence of reasonable alternatives, data on the likely risks and potential health benefits; rigorous oversight; and comprehensive plans for long-term, multi-generational follow-up.

The committee also called for broad public education and engagement in applying societal values to the risks and benefits of gene editing technologies.

In the months since the Washington summit, the development of a gene-editing tool called Crispr-Cas9 has made addressing the ethical issues surrounding human gene editing urgent.

As human genome editing becomes more effective, clinicians working in countries with few regulations will likely begin modifying embryos and implanting them in patients, raising the potential for inheritance of unintended mutations along with targeted changes, Charo said.

We are very much aware that medical tourism is a fact of global life now, she said. We certainly don't want to see the same thing, and a prohibition might exacerbate the problem.

Scheufele, a social scientist who studies communication and public understanding of science, spoke to the importance of public debate on the ethical issues involved.

We want to bring in people even if they know little about the topic and get them to the point where they can engage in meaningful debate, Scheufele said. We want to move forward in a responsible fashion with the best available science and a meaningful understanding of the risks and benefits.

The report also established a set of broad governance principles with respect to human genome editing in the U.S. and elsewhere: promote well-being, transparency, due care, responsible science, respect for persons, fairness and transnational cooperation.

Every country struggles with the same set of complexities but has a different regulatory system. So, we established larger principles that are applicable across different political or cultural contexts, Scheufele said.

While the National Academies panel drew a bright line between gene modification for treatment of disease and gene modification for enhancement, the boundary often is not clear, say opponents of human germ line editing.

This opens the door to advertisements from fertility clinics of giving your child the best start in life with a gene-editing packet, Marcy Darnovsky of the Center for Genetics and Society, a public interest group in Berkeley, Calif., told the New York Times. And whether these are real advantages or perceived advantages, they would accrue disproportionately to people who are already advantaged.

The new guidelines, Darnovsky noted, also set the United States apart from many European countries that have signed a treaty to refrain from human germ line editing.

George Church, co-founder of the gene-editing company Editas Medicine, told Wired that the line between treatment and enhancement will be hard to hit.

In the process of fixing something that is broken, you can move it to the middle of the bell curve or beyond, said Church, a geneticist at Harvard and MIT. If you are aiming at the middle, you will fall on the low or the high side.

Church isnt worried about athletes using Crispr-based therapies, he said the big market is aging adults who want to put off the effects of old age. If you want to be useful longer or do age reversal, that could be preventive medicine, he said. But if a therapy was sufficiently good, it would be enhancement.

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UW's Alta Charo: Gene editing for inherited human traits 'not ready now, might be in future' - The Courier Life News

A study from Massachusetts General Hospital (MGH) researchers has found that a pattern of gene variants associated with an "apple-shaped" body type, in which weight is deposited around the abdomen, rather than in the hips and thighs, increases the risk for type 2 diabetes and coronary heart disease, as well as the incidence of several cardiovascular risk factors. The report appears in the February 14 issue of JAMA.

"People vary in their distribution of body fat -- some put fat in their belly, which we call abdominal adiposity, and some in their hips and thighs," says Sekar Kathiresan, MD, director of the MGH Center for Genomic Medicine, associate professor of Medicine at Harvard Medical School, and senior author of the JAMA report. "Abdominal adiposity has been correlated with cardiometabolic disease, but whether it actually has a role in causing those conditions was unknown. We tested whether genetic predisposition to abdominal adiposity was associated with the risk for type 2 diabetes and coronary heart disease and found that the answer was a firm 'yes'."

While several observational studies have reported greater incidence of type 2 diabetes and heart disease among individuals with abdominal adiposity, they could not rule out the possibility that lifestyle factors -- such as diet, smoking and a lack of exercise -- were the actual causes of increased disease risk. It also could have been possible that individuals in the early stages of heart disease might develop abdominal adiposity because of a limited ability to exercise. The current study was designed to determine whether body type really could increase cardiometabolic risk.

To answer that question, the research team applied a genetic approach called mendelian randomization, which measures whether inherited gene variants actually cause outcomes such as the development of a disease. Using data from a previous study that identified 48 gene variants associated with waist-to-hip ratio adjusted for body mass index -- an established measure for abdominal adiposity -- they developed a genetic risk score. They then applied that score to data from six major genome-wide association studies and to individual data from the U.K. Biobank -- a total research group of more than 400,000 individuals -- to determine any association between a genetic predisposition to abdominal adiposity and cardiometabolic disease and its risk factors.

The results clearly indicated that genetic predisposition to abdominal adiposity is associated with significant increases in the incidence of type 2 diabetes and coronary heart disease, along with increases in blood lipids, blood glucose and systolic blood pressure. No association was found between the genetic risk score and lifestyle factors, and testing confirmed that only the abdominal adiposity effects of the identified gene variants were associated with cardiometabolic risk.

"These results illustrate the power of using genetics as a method of determining the effects of a characteristic like abdominal adiposity on cardiometabolic outcomes," says lead author Connor Emdin, DPhil, of the MGH Center for Genomic Medicine and the Cardiology Division. "The lack of association between the body type genetic risk score and confounding factors such as diet and smoking provides strong evidence that abdominal adiposity itself contributes to causing type 2 diabetes and heart disease."

Emdin continues, "Not only do these results allow us to use body shape as a marker for increased cardiometabolic risk, they also suggest that developing drugs that modify fat distribution may help prevent these diseases. Future research also could identify individual genes that could be targeted to improve body fat distribution to reduce these risks."

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Gene variants associated with body shape increase risk of heart disease, type 2 diabetes - Science Daily

February 15, 2017 Dr. Madhavan Nair oversees work in his lab at Herbert Wertheim College of Medicine. Credit: Florida International University

Opiate abuse is a significant risk factor for HIV infection, and in combination they can have a devastating effect on the brain. Scientists at FIU Herbert Wertheim College of Medicine (HWCOM) are studying new therapies that can short-circuit HIV infection and mitigate the damaging effects that opiate addiction has on the central nervous system.

The ambitious $3.5 million five-year study, funded by the National Institutes for Health is now underway and will be completed b7 2021. Researchers hope the work will lead to lead to a multi-purpose platform for drugs targeting a variety of other difficult to treat diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's and Huntington's diseases.

The Institute of Neuro-Immune Pharmacology at HWCOM, led by Chair and Associate Dean of the Department of Immunology Madhavan Nair, is teaming up with Kamel Khalili, chair of the Department of Neuroscience at Temple University, and the Comprehensive NeuroAIDS Center at Temple University's Lewis Katz School on a new study that will combine Khalil's gene editing strategy using nanotechnology with Nair's work to help opiate users with HIV.

Despite significant advances in anti-retroviral therapy (ART), which is used to treat HIV patients, ART is unable to penetrate the blood brain barrier (BBB) after systemic administration. In addition, the elimination of HIV from the central nervous system and peripheral reservoirs remains challenging due to the HIV genome's ability to integrate itself into the host genome.

But advances in nanotechnology have expanded the possibilities for novel drug delivery systems that can cross the BBB to recognize and eradicate HIV in the brain. Nair and other scientists from the Institute of Neuro-Immune Pharmacology at HWCOM have combined nanotechnology with magneto electro nanoparticles (MENPs) as externally field triggered/controlled drug carriers that offer the unique capability of low energy and dissipation free on-demand drug release across the BBB.

Nair's MENP drug-based delivery system is now the basis for the partnership with Khalili, who developed the Cas9/gRNA system; a genetic engineering tool that has shown great promise in finding and destroying copies of HIV that have burrowed into the host's genome.

The partnership will use Cas9/gRNA to eliminate entire integrated copies of the HIV genome from the host chromosome with the MENP drug-based delivery system.

"This is the first time that we are sending medicine to the brain that will eliminate latent HIV as well as deliver a morphine antagonist (methylnaltrexone) across the BBB in a non-invasive manner to protect neurons from morphine induced neurodegenerative effects," Nair says. MENP is non-invasive and fast-acting, and this newly created multi-disciplinary approach will also introduce unprecedented 3-D diagnostic views and allow clearance of the nanoparticles from the brain to the periphery by reverse external magnetic force once the cargo has been delivered.

Explore further: New nanotechnique to deliver life-saving drugs to the brain

(Phys.org) In a study published in today's issue of Nature Communications, researchers from FIU's Herbert Wertheim College of Medicine describe a revolutionary technique they have developed that can deliver and fully release ...

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Nanotechnology based gene editing to eradicate HIV brain reservoir in drug abusers - Phys.Org

February 14, 2017

A study from Massachusetts General Hospital (MGH) researchers has found that a pattern of gene variants associated with an "apple-shaped" body type, in which weight is deposited around the abdomen, rather than in the hips and thighs, increases the risk for type 2 diabetes and coronary heart disease, as well as the incidence of several cardiovascular risk factors. The report appears in the February 14 issue of JAMA.

"People vary in their distribution of body fat - some put fat in their belly, which we call abdominal adiposity, and some in their hips and thighs," says Sekar Kathiresan, MD, director of the MGH Center for Genomic Medicine, associate professor of Medicine at Harvard Medical School, and senior author of the JAMA report. "Abdominal adiposity has been correlated with cardiometabolic disease, but whether it actually has a role in causing those conditions was unknown. We tested whether genetic predisposition to abdominal adiposity was associated with the risk for type 2 diabetes and coronary heart disease and found that the answer was a firm 'yes'."

While several observational studies have reported greater incidence of type 2 diabetes and heart disease among individuals with abdominal adiposity, they could not rule out the possibility that lifestyle factors - such as diet, smoking and a lack of exercise - were the actual causes of increased disease risk. It also could have been possible that individuals in the early stages of heart disease might develop abdominal adiposity because of a limited ability to exercise. The current study was designed to determine whether body type really could increase cardiometabolic risk.

To answer that question, the research team applied a genetic approach called mendelian randomization, which measures whether inherited gene variants actually cause outcomes such as the development of a disease. Using data from a previous study that identified 48 gene variants associated with waist-to-hip ratio adjusted for body mass index - an established measure for abdominal adiposity - they developed a genetic risk score. They then applied that score to data from six major genome-wide association studies and to individual data from the U.K. Biobank - a total research group of more than 400,000 individuals - to determine any association between a genetic predisposition to abdominal adiposity and cardiometabolic disease and its risk factors.

The results clearly indicated that genetic predisposition to abdominal adiposity is associated with significant increases in the incidence of type 2 diabetes and coronary heart disease, along with increases in blood lipids, blood glucose and systolic blood pressure. No association was found between the genetic risk score and lifestyle factors, and testing confirmed that only the abdominal adiposity effects of the identified gene variants were associated with cardiometabolic risk.

"These results illustrate the power of using genetics as a method of determining the effects of a characteristic like abdominal adiposity on cardiometabolic outcomes," says lead author Connor Emdin, DPhil, of the MGH Center for Genomic Medicine and the Cardiology Division. "The lack of association between the body type genetic risk score and confounding factors such as diet and smoking provides strong evidence that abdominal adiposity itself contributes to causing type 2 diabetes and heart disease."

Emdin continues, "Not only do these results allow us to use body shape as a marker for increased cardiometabolic risk, they also suggest that developing drugs that modify fat distribution may help prevent these diseases. Future research also could identify individual genes that could be targeted to improve body fat distribution to reduce these risks."

Explore further: Adiposity genetic risk score tied to cardiometabolic health

More information: JAMA, DOI: 10.1001/jama.2016.21042

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