Category Archives: Gene Medicine

PUBLIC RELEASE DATE:

8-Jan-2014

Contact: David McKeon DMckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY (January 8, 2014) Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute in collaboration with scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) successfully generated a stem cell model of familial Alzheimer's disease (FAD). Using this stem cell model, researchers identified fourteen genes that may be implicated in the disease and one gene in particular that shows the importance that inflammation may play in the brain of Alzheimer's patients.

In this study, published today in PLOS ONE, the team of scientists produced stem cells and neural precursor cells (NPCs), representing early neural progenitor cells that build the brain, from patients with severe early-onset AD with mutations in the Presenilin 1 (PSEN1) gene. These NPCs had elevated Abeta42/Abeta40 ratios, indicating elevation of the form of amyloid found in the brains of Alzheimer's patients. These levels were greater than those in adult cells that did not have the PSEN1mutation. This elevated ratio showed that these NPCs grown in the petri dish were accurately reflecting the cells in the brains of FAD patients.

"Our ability to accurately recapitulate the disease in the petri dish is an important advance for this disease. These genes provide us with new targets to help elucidate the cause of sporadic forms of the disease as well provide targets for the discovery of new drugs," said Susan L. Solomon, Chief Executive Officer of The New York Stem Cell Foundation.

"The gene expression profile from Noggle's familial Alzheimer's stem cells points to inflammation which is especially exciting because we would not usually associate inflammation with this particular Alzheimer's gene. The greatest breakthroughs come with 'unknown unknowns', that is, things that we don't know now and that we would never discover through standard logic," said Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry and Director of the Center for Cognitive Health at the Icahn School of Medicine at Mount Sinai and a co-author on the study. Gandy is also Associate Director of the NIH-Designated Mount Sinai Alzheimer's Disease Research Center.

The researchers generated induced pluripotent stem (iPS) cells from affected and unaffected individuals from two families carrying PSEN1 mutations. After thorough characterization of the NPCs through gene expression profiling and other methods, they identified fourteen genes that behaved differently in PSEN1 NPCs relative to NPCs from individuals without the mutation. Five of these targets also showed differential expression in late onset Alzheimer's disease patients' brains. Therefore, in the PSEN1 iPS cell model, the researchers reconstituted an essential feature in the molecular development of familial Alzheimer's disease.

Although the majority of Alzheimer's disease cases are late onset and likely result from a mixture of genetic predisposition and environmental factors, there are genetic forms of the disease that affect patients at much earlier ages. PSEN1 mutations cause the most common form of inherited familial Alzheimer's disease and are one hundred percent penetrant, resulting in all individuals with this mutation getting the disease.

The identification of genes that behaved differently in patients with the mutation provides new targets to further study and better understand their effects on the development of Alzheimer's disease. One of these genes, NLRP2, is traditionally thought of as an inflammatory gene.

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Stem cell research identifies new gene targets in patients with Alzheimer's disease

PUBLIC RELEASE DATE:

8-Jan-2014

Contact: Darrell E. Ward Darrell.Ward@osumc.edu 614-293-3737 Ohio State University Wexner Medical Center

COLUMBUS, Ohio Currently, doctors use chromosome markers and gene mutations to determine the best treatment for patients with acute myeloid leukemia (AML). But a new study suggests that a score based on seven mutated genes and the epigenetic changes that the researchers discovered were also present might help guide treatment by identifying novel subsets of patients.

The findings, published in the Journal of Clinical Oncology, come from a study led by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James).

The epigenetic change used in the study is DNA methylation. It involves the addition of methyl groups to DNA, which can reduce or silence a gene's activity, or expression. Abnormal DNA methylation alters normal gene expression and often plays an important role in cancer development.

Overall, the findings suggest that patients with a low score indicating that one or none of the seven genes is overexpressed in AML cells had the best outcomes, and that patients with high scores that is, with six or seven genes highly expressed had the poorest outcomes.

"To date, disease classification and prognostication for AML patients have been based largely on chromosomal and genetic markers," says principal investigator Clara D. Bloomfield, MD, Distinguished University Professor, Ohio State University Cancer Scholar and Senior Adviser.

"Epigenetic changes that affect gene expression have not been considered. Here we show that epigenetic changes in previously recognized and prognostically important mutated genes can identify novel patient subgroups, which might better help guide therapy," says Bloomfield, who is also the William Greenville Pace III Endowed Chair in Cancer Research at Ohio State.

The seven-gene panel was identified in 134 patients aged 60 and older with cytogenetically normal acute myeloid leukemia (CN-AML) who had been treated on Cancer and Leukemia Group B (CALGB)/Alliance clinical trials.

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AML score that combines genetic and epigenetic changes might help guide therapy

Current ratings for: Single faulty gene causes major type 2 diabetes symptom in mice

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New research from the US reported in the journal Diabetes, shows that the loss of just one gene in mice is enough to cause fasting hyperglycemia - a major symptom of type 2 diabetes.

In their paper, researchers from the College of Medicine at the University of Illinois at Chicago (UIC) explain how malfunctions in insulin-producing pancreatic beta cells is a common feature of type 2 diabetes.

Lead author Bellur S. Prabhakar, professor and head of microbiology and immunology at UIC, says they found that when a gene called MADD is not working properly, insulin is not released into the bloodstream. Lack of insulin means the body is unable to regulate blood sugar or glucose - a major feature of diabetes.

About 8% of Americans and more than 360 million people around the world have type 2 diabetes, a disease that in turn can lead to more serious conditions like cardiovascular disease, kidney failure, blindness, and loss of limbs.

In healthy people without diabetes, the beta cells of the pancreas release insulin into the bloodstream to help regulate blood sugar levels which rise after eating.

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Single faulty gene causes major type 2 diabetes symptom in mice

PUBLIC RELEASE DATE:

6-Jan-2014

Contact: Anita Srikameswaran 412-578-9193 University of Pittsburgh Schools of the Health Sciences

PITTSBURGH, Jan. 6, 2014 The increased activation of a key oncogene in head and neck cancers could be the result of mutation and dysfunction of regulatory proteins that are supposed to keep the gene, which has the potential to cause cancer, in check, according to a new study led by researchers at the University of Pittsburgh School of Medicine. The findings, published in the early online version of the Proceedings of the National Academy of Sciences, suggest a new target for drugs to treat head and neck tumors, as well as other cancers.

Many research teams have found activation and increased signaling of a protein known as Signal Transducer and Activator of Transcription 3 (STAT3) in different kinds of cancers, and it is associated with poor prognosis, said senior author Jennifer Grandis, M.D., Distinguished Professor of Otolaryngology, Pitt School of Medicine, and director of the Head and Neck Program at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter. In adult tissues, STAT3 triggers the production of other proteins that promote the growth and survival of cancer cells.

"Until now, the question of why STAT3 could be hyperactivated has gone unanswered," Dr. Grandis said. "Our findings reveal a possible mechanism for this abnormal activity, which could help us develop new cancer drugs."

Noting that gene aberrations in STAT3 itself rarely occurred in head and neck cancers, she and her colleagues looked for mutations in other proteins associated with increased activity of STAT3. To be activated, STAT3 must be phosphorylated, meaning a phosphate group is added to it. Many cancer drugs work by inhibiting enzymes called kinases that encourage this process. The team focused instead on the other side of the biochemical seesaw in which enzymes called phosphatases deactivate proteins by removing phosphates.

To their surprise, they found head and neck tumors with elevated STAT3 were associated with mutations in the PTPR family of phosphatases. When they reproduced the mutations in computational and lab models, they saw that they led to dysfunction of the enzymes.

"Because the phosphatases don't work properly, phosphate groups don't get removed from STAT3 appropriately, and it stays activated," Dr. Grandis explained. "These mutations essentially get rid of the brakes that might otherwise slow or even stop cancer development."

It might be possible one day to screen tumors for mutations in the PTPR group and then treat them with drugs that inhibit STAT3's activity, she added.

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No 'brakes' -- Study finds mechanism for increased activity of oncogene in certain cancers

As scientists get closer to using embryonic stem cells in new treatments for blindness, spinal cord injuries and heart disease, a U.S. legal debate could determine who profits from that research.

Consumer Watchdog, a nonprofit advocacy group, wants an appeals court to invalidate a University of Wisconsin-Madisons patentfor stem cells derived from human embryos, saying its too similar to earlier research. The Santa Monica, California, group also says the U.S. Supreme Courts June ruling limiting ownership rights of human genes should apply to stem cells, a potentially lucrative field for medical breakthroughs.

The challenge to Wisconsin Alumni Research Foundation, the universitys licensing arm, is about whether patents help or hinder U.S. stem-cell research, which has been stymied by political debate. The consumer group says it drives up the cost of research by requiring companies and some academics to pay a licensing fee to the university.

What were asking the government to do is say WARF has no right to the patent, said Dan Ravicher, executive director Public Patent Foundation in New York, which is handling the challenge for Consumer Watchdog. Its like the government sent a check to WARF they didnt deserve.

Consumer Watchdog lost a challenge at the U.S. Patent and Trademark Office in January 2013. It wants the Court of Appeals for the Federal Circuit in Washington to review that decision and consider new arguments based on the Supreme Courts finding that genes -- like stem cells -- are a natural material that cant be patented. Beyond the science question, the case has become a flashpoint over how far members of the public can go to invalidate patents on policy grounds.

While the patent expires in April 2015 and the university has other stem-cell-related patents, Consumer Watchdog is continuing a six-year battle to invalidate it because stem-cell research is starting to get some traction into therapeutic uses, Ravicher said.

The promise of embryonic stem cells is to create or repair tissues and organs using material taken from eggs fertilized in the laboratory. The cells created can be replicated indefinitely, and with the right biological cues, may aid in treating damaged heart tissue and spinal cords, or generate therapies for diabetes and cancer. Companies like StemCells Inc. (STEM) and Advanced Cell Technology Inc. are testing therapies to treat macular degeneration, a cause of blindness.

The next paradigm shift in medicine will be advances in cell therapy -- its under way, said Jason Kolbert, senior biotechnology analyst with Maxim Group LLC in New York. He said pharmaceutical makers such as Teva Pharmaceutical Industries Ltd. (TEVA) of Petach Tikva, Israel, and Pfizer (PFE) Inc. of New York are working with stem-cell researchers on new therapies.

Stem-cell science in the U.S. was curbed in 2001 when then-President George W. Bush issued an executive order limiting research to existing cell lines amid controversy over human embryo destruction, even though they were never in a womans uterus. President Barack Obama reversed that order in 2009.

Some scientists have avoided the public debate by using adult cells to find the unlimited potential they have in embryonic cells.

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Gene Patent Case Fuels U.S. Court Test of Stem Cell Right

A study that made its way from the Middle East to New York has identified a gene mutation found in those of African descent, shedding some light on why a significant number of black people are predisposed to certain diseases. NY1's Erin Billups filed the following report.

Too much fat or triglycerides in the blood stream leads to heart disease, type 2 diabetes, obesity and stroke are all diseases that are are found at higher rates among people of African ancestry.

Ronald Crystal, chair of Genetic Medicine at Weill Cornell Medical College, says they've found a genetic variation they believe is partially responsible.

"When we looked at the medical literature we found that it had been discovered 20 years ago but was thought to be a very rare mutation," says Dr. Crystal.

It turned out this mutation of a protein gene called Apo-E was relatively common among people native to the Middle Eastern country Qatar.

"Apo-E is a gene that we all have. It codes for a protein that helps us carry fats in our blood," explains Dr. Crystal.

The mutation they discovered in Qatari with African ancestry increases the amount of fat in the blood.

"So we then looked in Africans, and we found that in fact the mutation was pretty common in the Africans as well. Then we transferred the concept to New York. And it turns out it was pretty common in African Americans," says Dr. Crystal.

They looked at the DNA of 2,000 black New Yorkers, the largest study of the three.

"What it means is that four out of 100 New York African Americans have a mutation that will increase the levels of fats, specifically triglycerides in their blood. It's a mild increase, and it's only one little part of the whole puzzle," explains Dr. Crystal.

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Gene Mutation Increases Certain Health Risks For Blacks, Study Finds

Gene therapy carries the promise of cures for many diseases and for types of medical treatment most of us would not have thought possible. With its potential to eliminate and prevent hereditary diseases such as cystic fibrosis and hemophilia and its use as a possible cure for heart disease, AIDS, and cancer, gene therapy is a potential medical miracle-worker.

But what about gene therapy for children? There's a fair amount of risk involved in trials of this kind of therapy, and to date, only kids who are seriously ill or have illnesses incurable by conventional means have been involved in clinical trials using gene therapy.

For those with serious illnesses that aren't responsive to conventional therapies, however, gene therapy may soon offer hope that didn't exist just a short time ago.

Our genes are part of what makes us unique. Inherited from our parents, they go far in determining our physical traits like the color of our eyes and the color and texture of our hair. They also determine things like whether babies will be male or female, the amount of oxygen blood can carry, and IQ.

Genes are composed of strands of a molecule called DNA and are located in single file within the chromosomes. The genetic message is encoded by the building blocks of the DNA, which are called nucleotides. Approximately 3 billion pairs of nucleotides are in the chromosomes of a human cell, and each person's genetic makeup has a unique sequence of nucleotides. This is mainly what makes us different from one another.

Scientists believe that every human has about 25,000 genes per cell. A mutation, or change, in any one of these genes can result in a disease, physical disability, or shortened life span. These mutations can be passed from one generation to another, inherited just like a mother's red hair or a father's brown eyes. Mutations also can occur spontaneously in some cases, without having been passed on by a parent. With gene therapy, the treatment or elimination of inherited diseases or physical conditions due to these mutations could become a reality.

Gene therapy involves the manipulation of genes to fight or prevent diseases. Put simply, it introduces a "good" gene into a person who has a disease caused by a "bad" gene.

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KidsHealth for Parents - Gene Therapy and Children

At the forefront of medicine, Gene Therapy brings you the latest research into genetic and cell-based technologies to treat disease. It also publishes Progress & Prospects reviews and News and Commentary articles, which highlight the cutting edge of the field.

Volume 21, No 1 January 2014 ISSN: 0969-7128 EISSN: 1476-5462

2012 Impact Factor 4.321* 70/290 Biochemistry & Molecular Biology 22/159 Biotechnology & Applied Microbiology 33/161 Genetics & Heredity 25/121 Medicine, Research & Experimental

Editors: J Glorioso, USA N Lemoine, UK

*2012 Journal Citation Reports Science Edition (Thomson Reuters, 2013)

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Gene Therapy now offers authors the option to publish their articles with immediate open access upon publication. Open access articles will also be deposited on PubMed Central at the time of publication and will be freely available immediately. Find out more from our FAQs page.

Reviews by top researchers in the field. See the recent Progress and Prospects articles.

Essential topics explored in depth in Gene Therapy Special Issues.

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Gene Therapy - Nature

Gene medicine is making breakthroughs for health questions that have baffled humanity for centuries. Gene therapy is the applicable aspect of the science of gene medicine. Treatments are being developed that can reverse genetic diseases at the molecular level. Health questions that have previously be unanswered are now being solved. Health questions like how to remedy chronic pain are now being clinically tested and the gene therapy is already showing substantial subsiding of pain for the clinical trial patients. As countries put more funding into gene medicine, and more collaboration takes place between those countries, many of the health questions that we have today will be answered in the next decade

Gene medicine is one of the medical disciplines that affect all aspects of human health. From allergies, bone growth and cell development. Gene medicine is also one of the most mysterious to those with health questions as the science is only recognized in the media when discoveries are made. However, research is going on everyday in the field of gene medicine and breakthroughs, while they dont happen everyday, are happening more often. Gene medicine is beginning to look deeper into how dieseases can be blocked, removed and altered using our own human chemistry. Those with health questions and that want to find out more can read any number of medical periodicals that are being released every month. To read the latest news about health and medicine go here

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Gene Medicine and Health

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Researchers from the University of Illinois at Chicago College of Medicine have found that dysfunction in a single gene in mice causes fasting hyperglycemia, one of the major symptoms of type 2 diabetes. Their findings were reported online in the journal Diabetes.

If a gene called MADD is not functioning properly, insulin is not released into the bloodstream to regulate blood sugar levels, says Bellur S. Prabhakar, professor and head of microbiology and immunology at UIC and lead author of the paper.

Type 2 diabetes affects roughly 8 percent of Americans and more than 366 million people worldwide. It can cause serious complications, including cardiovascular disease, kidney failure, loss of limbs and blindness.

In a healthy person, beta cells in the pancreas secrete the hormone insulin in response to increases in blood glucose after eating. Insulin allows glucose to enter cells where it can be used as energy, keeping glucose levels in the blood within a narrow range. People with type 2 diabetes dont produce enough insulin or are resistant to its effects. They must closely monitor their blood glucose throughout the day and, when medication fails, inject insulin.

In previous work, Prabhakar isolated several genes from human beta cells, including MADD, which is also involved in certain cancers. Small genetic variations found among thousands of human subjects revealed that a mutation in MADD was strongly associated with type 2 diabetes in Europeans and Han Chinese.

People with this mutation had high blood glucose and problems of insulin secretion the "hallmarks of type 2 diabetes, Prabhakar said. But it was unclear how the mutation was causing the symptoms, or whether it caused them on its own or in concert with other genes associated with type 2 diabetes.

To study the role of MADD in diabetes, Prabhakar and his colleagues developed a mouse model in which the MADD gene was deleted from the insulin-producing beta cells. All such mice had elevated blood glucose levels, which the researchers found was due to insufficient release of insulin.

We didnt see any insulin resistance in their cells, but it was clear that the beta cells were not functioning properly, Prabhakar said. Examination of the beta cells revealed that they were packed with insulin. The cells were producing plenty of insulin, they just werent secreting it, he said.

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Loss of Function of a Single Gene Linked to Diabetes in Mice