Category Archives: Gene Medicine

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As scanning genomes for disease-related gene variations becomes more commonplace, scientists are pinpointing gene variations that change the way proteins function. Using this approach, a new study found a previously unknown gene variation that appears to make blood lipid levels healthier in humans and reduce risk of heart attacks.

The study researchers, from the University of Michigan and the Norwegian University of Science and Technology, report their findings in Nature Genetics. They hope the discovery will lead to new ways of testing or treating patients with high cholesterol and other lipid disorders.

They explain that by looking at the genetic code differently - such as looking for how it influences the way proteins behave - they found the gene hiding in plain sight in previous searches for cardiovascular risk genes.

Senior author Cristen Willer, assistant professor of Internal Medicine, Human Genetics and Computational Medicine & Bioinformatics at the University of Michigan Medical School, says:

"While genetic studies that focused on common variations may explain as much as 30% of the genetic component of lipid disorders, we still don't know where the rest of the genetic risk comes from. This approach of focusing on protein-changing variation may help us zero in on new genes faster."

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New gene-scanning approach finds link to heart attack risk 'hiding in plain sight'

PUBLIC RELEASE DATE:

16-Mar-2014

Contact: Kara Gavin kegavin@umich.edu 734-764-2220 University of Michigan Health System

ANN ARBOR, Mich. Scientists have discovered a previously unrecognized gene variation that makes humans have healthier blood lipid levels and reduced risk of heart attacks -- a finding that opens the door to using this knowledge in testing or treatment of high cholesterol and other lipid disorders.

But even more significant is how they found the gene, which had been hiding in plain sight in previous hunts for genes that influence cardiovascular risk.

This region of DNA where it was found had been implicated as being important in controlling blood lipid levels in a report from several members of the same research team in 2008. But although this DNA region had many genes, none of them had any obvious link to blood lipid levels. The promise of an entirely new lipid-related gene took another six years and a new approach to find.

In a new paper in Nature Genetics, a team from the University of Michigan and the Norwegian University of Science and Technology report that they zeroed in on the gene in an entirely new way.

The team scanned the genetic information available from a biobank of thousands of Norwegians, focusing on variations in genes that change the way proteins function. Most of what they found turned out to be already known to affect cholesterol levels and other blood lipids.

But one gene, dubbed TM6SF2, wasn't on the radar at all. In a minority of the Norwegians who carried a particular change in the gene, blood lipid levels were much healthier and they had a lower rate of heart attack. And when the researchers boosted or suppressed the gene in mice, they saw the same effect on the animals' blood lipid levels.

"Cardiovascular disease presents such a huge impact on people's lives that we should leave no stone unturned in the search for the genes that cause heart attack," says Cristen Willer, Ph.D., the senior author of the paper and an assistant professor of Internal Medicine, Human Genetics and Computational Medicine & Bioinformatics at the U-M Medical School.

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Novel gene-finding approach yields a new gene linked to key heart attack risk factor

Sunday, March 16, 2014

Eugene Gene Schroeder Fick died March 8, 2014, in Clearwater, Fla.

Gene was born Aug. 19, 1924, to George A. and Josephine J. Fick in Tomah, Wis. His father was killed by lightning while trout fishing.

His family moved to La Crosse, Wis., where Gene attended German Lutheran School, graduating from Logan High School. Genes physical size and strength helped him become a star football and basketball player, which earned him a college scholarship. However, World War II intervened; he served in Company C Signal Corps in France, Germany and Japan.

After being honorably discharged, Gene enrolled in college now known as the University of Wisconsin-Stevens Point where he excelled in football and basketball. Sports did not consume all of Genes interest, as fellow student, Mary Noble, won his heart. On Aug. 20, 1949, they were married at the Methodist Church.

Gene, fatherless from age 4, and Marys father, Harrison Noble, easily connected. While still in college, Noble offered Gene the position of managing the Noble Hatchery. Gene gladly accepted.

Daughters, Terrie and Mary, and son, George, were born. George was diagnosed with Downs syndrome, so the familys focus changed with his birth. Gene worked long days at the Noble Hatchery, sharing time with his children at night as Mary re-entered the University of Wisconsin-Stevens Point to study speech therapy.

Gene was instrumental in creating the Sheltered Workshop in Stevens Point, which evolved into Community Industries Corp. under his guidance as president and director. He and Mary helped to develop a local preschool for handicapped children; Gene served as president of the Portage County Handicapped Childrens Association. He was active in the Evening Lions Club, Izaak Walton League and ELKS. He was president and member of the Stevens Point South Side Business Association.

Gene had a deep love for conservation and outdoors activities. Beginning in 1962, he camped with his family each summer, discovering the Snowy Range in 1965. They returned each year, making many friends in Centennial. For 20 years, Gene and Mary volunteered as campground hosts in Medicine Bow National Forest. They eventually built a home in Centennial to comfortably enjoy Genes passion: hunting and fishing. Since 2007, Genes health had declined and the family enjoyed warmer winters in Oldsmar, Fla.

Gene is survived by Mary, his wife of 64 years; daughters, Terrie (husband Randy) Groshek and Mary Fick Monteith; son George Fick; grandchildren, Steven Groshek and Allison (husband Ahren) Schaefer; great-grandson Kayden Schaefer; and sister Joanne (husband Raymond) Zimmerman. He was preceded in death by his father; mother; and sister Shirley Linhart.

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Eugene Gene Schroeder Fick

PUBLIC RELEASE DATE:

13-Mar-2014

Contact: Stephanie Desmon sdesmon1@jhmi.edu 410-955-8665 Johns Hopkins Medicine

In a series of experiments sparked by fruit flies that couldn't sleep, Johns Hopkins researchers say they have identified a mutant gene dubbed "Wide Awake" that sabotages how the biological clock sets the timing for sleep. The finding also led them to the protein made by a normal copy of the gene that promotes sleep early in the night and properly regulates sleep cycles.

Because genes and the proteins they code for are often highly conserved across species, the researchers suspect their discoveries boosted by preliminary studies in mice could lead to new treatments for people whose insomnia or off-hours work schedules keep them awake long after their heads hit the pillow.

"We know that the timing of sleep is regulated by the body's internal biological clock, but just how this occurs has been a mystery," says study leader Mark N. Wu, M.D., Ph.D., an assistant professor of neurology, medicine, genetic medicine and neuroscience at the Johns Hopkins University School of Medicine. "We have now found the first protein ever identified that translates timing information from the body's circadian clock and uses it to regulate sleep."

A report on the work appears online March 13 in the journal Neuron.

In their hunt for the molecular roots of sleep regulation, Wu and his colleagues studied thousands of fruit fly colonies, each with a different set of genetic mutations, and analyzed their sleep patterns. They found that one group of flies, with a mutation in the gene they would later call Wide Awake (or Wake for short), had trouble falling asleep at night, a malady that looked a lot like sleep-onset insomnia in humans. The investigators say Wake appears to be the messenger from the circadian clock to the brain, telling it that it's time to shut down and sleep.

After isolating the gene, Wu's team determined that when working properly, Wake helps shut down clock neurons of the brain that control arousal by making them more responsive to signals from the inhibitory neurotransmitter called GABA. Wake does this specifically in the early evening, thus promoting sleep at the right time. Levels of Wake cycle during the day, peaking near dusk in good sleepers.

Flies with a mutated Wake gene that couldn't get to sleep were not getting enough GABA signal to quiet their arousal circuits at night, keeping the flies agitated.

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Researchers identify gene that helps fruit flies go to sleep

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Newswise More than 1,400 sports medicine physicians from the United States and abroad will attend the 23rd Annual Meeting of the American Medical Society for Sports Medicine (AMSSM), the largest primary care sports medicine physician organization in the nation. For more info, visit http://www.amssm.org. A full program can be accessed here: http://www.amssm.org/Content/pdf%20files/2014_AM-Brochure.pdf

The meeting will reveal cutting-edge medical research and serve as a platform to address current and controversial issues in the field of sports medicine.

Keynotes will address genetics and training in athletics, youth sports challenges, post-concussion syndrome, exercise and aging, international perspectives on challenging musculoskeletal injuries and more.

WHERE: Hyatt Regency New Orleans,601 Loyola Ave., New Orleans, LA 70113

DATE: Saturday, April 5 Wednesday, April 9, 2014

PRESIDENTIAL KEYNOTE: David Epstein, Author of The Sports Gene Sunday, April, 6, 10:40 a.m. 11:10 a.m.

INTERNATIONAL KEYNOTES: Prof Mark E. Batt, MB BChir, MRCGP, DM (United Kingdom) Peter Brukner, MBBS (Australia) Peter Fricker, MBBS (Australia) Mark Tarnopolsky, MD, PhD (Canada)

NOTE TO PRESS: Media interested in being credentialed for the 2014 AMSSM Annual Meeting must contact Jessica Torres-Sosa, jtorres@amssm.org, 913.909.9878. Media guidelines: http://www.amssm.org/Content/pdf%20files/MediaRoom_Guidelines.pdf

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New Sports Medicine Research Revealed, Internationally Recognized Leaders to Deliver Keynotes at 2014 AMSSM Annual ...

The gene known to be associated with breast cancer susceptibility, BRCA 1, plays a critical role in the normal metabolic function of skeletal muscle, according to a new study led by University of Maryland School of Public Health researchers. Dr. Espen Spangenburg, associate professor of kinesiology, and his laboratory team are the first to identify that the BRCA1 protein is expressed in the skeletal muscle of both mice and humans, and that it plays a key role in fat storage, insulin response and mitochondrial function in skeletal muscle cells. The research is published in the Journal of Lipid Research.

"Our findings suggest that certain mutations in the BRCA1 gene may put people at increased risk for metabolic diseases like obesity and type 2 diabetes," said Dr. Spangenburg. "Without BRCA1, muscle cells store excess fat and start to look diabetic. We believe that the significance of the BRCA1 gene goes well beyond breast cancer risk."

Dr. Spangenburg and colleagues, including researchers from the University of Maryland School of Medicine, Brigham Young University, Karolinska Institutet in Sweden, and East Carolina University, found that the BRCA1 protein exists in both mouse and in human skeletal muscle. This is the first evidence since the discovery of BRCA1 in 1994 that the gene is expressed in human muscle cells.

They further established that the protein produced by the BRCA 1 gene binds with a protein known to play an important role in the metabolism of fat in muscle cells known as Acetyl-CoA carboxylase or ACC. After a period of exercise, the BRCA 1 protein binds to ACC, which helps "turns it off." This deactivation of ACC encourages the utilization of fatty acids by the muscle.

Once they established that the two proteins complex together, they sought to answer if BRCA1 plays a critical role in regulating muscle metabolic function. To do so, they "knocked out" the gene so that it was no longer being expressed in the muscle cells cultured from healthy, active and lean female subjects. This was done using shRNA technology specific for BRCA1 in human myotubes (skeletal muscle fiber cells).

The result was that the muscle cells started to look diseased. The removal of BRCA1 from the cells, which simulated what could happen in the cells of a person with a BRCA1 mutation, resulted in increased lipid storage, decreased insulin signaling, reduced mitochondrial function and increased oxidative stress. These are all key risk factors for the development of metabolic diseases, such as obesity, type 2 diabetes and cardiovascular disease.

"Our findings make it clear that BRCA1 plays a protective role against the development of metabolic disease," Dr. Spangenburg explains. "This gene needs to be there, and should be considered a target to consider in the treatment of type 2 diabetes and/or obesity."

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The above story is based on materials provided by University of Maryland. Note: Materials may be edited for content and length.

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Breast cancer gene could play critical role in obesity, diabetes

PUBLIC RELEASE DATE:

10-Mar-2014

Contact: Sandy Van sandy@prpacific.com 808-526-1708 Cedars-Sinai Medical Center

LOS ANGELES (March 10, 2014) A team of researchers from the National Institutes of Health, Emory University and Cedars-Sinai specialists in identifying and treating very rare diseases used three innovative tools to detect a previously unknown gene mutation, test potential therapies in the lab, and initiate personalized drug treatment for a boy with a lifelong history of uncontrollable seizures that caused significant impact on his cognitive and social development.

"This personalized medical approach exemplifies the power of current research tools and shows the immense potential of applying these technologies for future patients," said Tyler Mark Pierson, MD, PhD, a pediatric neurologist and member of the Department of Pediatrics and the Department of Neurology at Cedars-Sinai. Pierson, a member of the research faculty at the Cedars-Sinai Regenerative Medicine Institute, is first author of an article in Annals of Clinical and Translational Neurology that published online March 3 ahead of print.

Pierson was a member of the National Institutes of Health's Undiagnosed Diseases Program when he was introduced to the patient and his family. The child was first seen at the NIH-UDP when he was 6; he was diagnosed with early-onset epileptic encephalopathy of unknown etiology. The patient had experienced treatment-resistant seizures since 3 months of age, which caused significant issues with brain development resulting in global developmental delay. The NIH-UDP is a program of NIH's National Human Genome Research Institute (NHGRI), Office of Rare Diseases Research, and Clinical Center.

The researchers identified a "de novo" gene mutation one that occurs for the first time in a member of a family in a gene called GRIN2A. The discovery required an analysis of the patient's genetic makeup in search of the one gene that changed, setting this detrimental series of events in motion. Pierson and his colleagues at the NIH-UDP and Emory University used a recently developed technique called exome sequencing, which focuses on this "functional" part of the genome. They further employed a unique set of data bases and "filters" to streamline their search and screen out false positive results, which are fairly common with new-generation technology that rapidly analyzes thousands of genetic sequences.

"Genome-scale sequencing is a powerful new tool in medical diagnostics. The data it returns, however, can be challenging to interpret, especially for ultra-rare disorders. The rapid bench-to-bedside story of the GRIN2A variation in this family is an example of the coalescence of expertise in medicine, medical genomics and basic science around a single child. This is the type of collaboration that will be needed in an age where we will struggle to connect vast data-collecting capability with the health of individual people," said David Adams, MD, PhD, pediatrician and biochemical geneticist at NHGRI.

Pierson added that many other genes have been associated with several forms of epilepsy in infancy, but only few other instances of early-onset epileptic encephalopathy involved the GRIN2A gene. The GRIN2A gene influences electrochemical events that affect the flow and strength of electrical impulses in the brain.

Having identified the de novo gene defect, the researchers conducted laboratory experiments to confirm the resulting protein dysfunction and its effects on electrical-regulating mechanisms.

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Detecting, testing, treating rare diseases: Technology delivers new era of personalization

China was the first country to approve a gene therapy product for commercial use, in 2004. The U.S. has yet to endorse any such treatments and the field has been plagued by carcinogenicity

Flickr/hermida

From Nature magazine

Europes drugs regulator has for the first time recommended a gene therapy medicine for approval.

Glybera, a treatment for patients who cannot produce enough of an enzyme crucial for breaking down fat, was backed by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP). This recommendation has to be endorsed by the European Commission before it becomes available, but it would be unusual for the Commission to reject the recommendation.

Gene therapy involves transferring genes into patients to treat their diseases. In this case Glybera uses a virus injected into a patient to deliver a working copy of a gene for producing lipoprotein lipase (LPL). LPL deficiency affect no more than one or two people in a million.

Back in 2004 China became the first country to approve a gene therapy product for commercial use, with a treatment for cancer. But Europe and the United States have yet to endorse any gene therapy treatments and the field has been plagued by issues such as carcinogenicity.

Jrn Aldag, chief executive of uniQure, the Amsterdam-based company that owns Glybera, says todays announcement from the EMA is an overdue signal to the gene therapy community that things are changing. It unlocks the potential, he told Nature. You will see more investment coming.

Fantastic news Tim Cot, former head of the US Food and Drug Administrations Office of Orphan Products Development and now an independent consultant, says the approval is "astounding, fantastic news. It puts Europe at the forefront.

Glybera had previously received negative opinions from both the CHMP and the EMA Committee for Advanced Therapies (CAT), which advises on cutting edge treatments. However, after re-evaluating the treatment in just those patients who experience severe or multiple attacks of pancreatitis as a result of LPL deficiency, the CAT gave a positive opinion in June, and this has now been endorsed by the CHMP.

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Europe Nears First Approval for Gene Therapy Treatment

The approach involves using enzymes to destroy a gene in the immune cells of people with HIV, thereby increasing resistance to the virus

Scanning electron micrograph of a human T cell from the immune system of a healthy donor. Credit:NIAID/NIH - Wikimedia Commons

A clinical trial has shown that a gene-editing technique can be safe and effective in humans. For the first time, researchers used enzymes called zinc-finger nucleases (ZFNs) to target and destroy a gene in the immune cells of 12 people with HIV, increasing their resistance to the virus. The findings were published March 5 in The New England Journal of Medicine.

This is the first major advance in HIV gene therapy since it was demonstrated that the Berlin patient Timothy Brown was free of HIV, says John Rossi, a molecular biologist at the Beckman Research Institute of the City of Hope National Medical Center in Duarte, California. In 2008, researchers reported thatBrown gained the ability to control his HIV infectionafter they treated him with donor bone-marrow stem cells that carried a mutation in a gene calledCCR5. Most HIV strains use a protein encoded byCCR5as a gateway into the T cells of a hosts immune system. People who carry a mutated version of the gene, including Brown's donor, are resistant to HIV.

But similar treatment isnot feasible for most people with HIV: it is invasive, and the body is likely to attack the donor cells. So a team led by Carl June and Pablo Tebas, immunologists at the University of Pennsylvania in Philadelphia, sought to create the beneficialCCR5 mutation in a persons own cells, using targeted gene editing.

Personalized medicine The researchers drew blood from 12 people with HIV who had been taking antiretroviral drugs to keep the virus in check. After culturing blood cells from each participant, the team used a commercially available ZFN to target theCCR5gene in those cells. The treatment succeeded in disrupting the gene in about 25% of each participants cultured cells; the researchers then transfused all of the cultured cells into the participants. After treatment, all had elevated levels of T cells in their blood, suggesting that the virus was less capable of destroying them.

Six of the 12 participants then stopped their antiretroviral drug therapy, while the team monitored their levels of virus and T cells. Their HIV levels rebounded more slowly than normal, and their T-cell levels remained high for weeks. In short, the presence of HIV seemed to drive the modified immune cells, which lacked a functionalCCR5gene, to proliferate in the body. Researchers suspect that the virus was unable to infect and destroy the altered cells.

They used HIV to help in its own demise, says Paula Cannon, who studies gene therapy at the University of Southern California in Los Angeles. They throw the cells back at it and say, Ha, now what?

Long-term action In this first small trial, the gene-editing approach seemed to be safe: Tebas says that the worst side effect was that the chemical used in the process made the patients bodies smell bad for several days.

The trial isnt the end game, but its an important advance in the direction of this kind of research, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Its more practical and applicable than doing a stem-cell transplant, he says, although it remains to be seen whether it is as effective.

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Gene-Editing Technique Shown to Work as HIV Treatment

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In a small trial, researchers have successfully used gene therapy to boost the immune system of 12 patients with HIV to resist infection. They removed the patients' white blood cells to edit a gene in them, then infused them back into the patients. Some of the patients who showed reduced viral loads were off HIV drugs completely.

In fact, one of the patients showed no detectable trace of HIV at all after therapy. The researchers, who report their phase I study in the New England Journal of Medicine believe theirs is the first published account of using gene editing in humans.

The team included researchers from the University of Pennsylvania (Penn), PA, Albert Einstein College of Medicine, Bronx, NY, and Sangamo BioSciences, Richmond, CA, the company that developed the gene editing technology.

Carl H. June, senior author of the study and professor at Penn's Perelman School of Medicine, says:

"This study shows that we can safely and effectively engineer an HIV patient's own T cells to mimic a naturally occurring resistance to the virus, infuse those engineered cells, have them persist in the body, and potentially keep viral loads at bay without the use of drugs."

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Gene therapy used to block HIV without drugs