By James Vicini

WASHINGTON | Mon Mar 26, 2012 7:58pm BST

WASHINGTON (Reuters) - The U.S. Supreme Court on Monday set aside a ruling that said Myriad Genetics Inc could patent two genes linked to breast and ovarian cancers, and ordered further review by a lower court in light of a conflicting ruling in a similar case.

The Myriad case has been closely watched by the biotechnology industry, with some insiders suggesting that a ruling against gene patenting could have a devastating effect on future innovation.

That includes the fledgling field of personalized medicine, which depends on genetic tests, such as those developed by Myriad, to match patients with specific therapies.

The justices delayed any action on the ruling by the U.S. Court of Appeals for the Federal Circuit that Myriad has the right to patent two human genes, known as BRCA1 and BRCA2, that account for most inherited forms of breast and ovarian cancers.

The Supreme Court ruled last week in a separate case involving medical diagnostics that companies cannot patent observations about a natural phenomenon. On Monday, it asked the lower court to revisit the Myriad case to view how it may or may not relate to that decision.

The move is expected to delay a verdict in the Myriad case by as much as several years. In the case of the individual company, that may give it enough time to benefit from the use of its contested patents. Shares in Myriad rose over 3 percent.

"Our intellectual property consultant could potentially see a scenario where the case doesn't move its way back to the Supreme Court for another 2 to 3 plus years, keeping the BRACAnalysis franchise safe from competition," said Junaid Husain, a research analyst for Dougherty & Co.

Women who test positive using Myriad's gene test, called BRACAnalysis, have an 82 percent higher risk of developing breast cancer and a 44 percent higher risk of ovarian cancer in their lifetimes. Such tests could help determine a future course of therapy.

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Myriad gene patent ruling sent back to lower court

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) The US Supreme Court is sending the most high-profile gene patenting case to date, focusing on Myriad Genetics' breast and ovarian cancer tests, back to a lower court for reconsideration in light of its decision last week to invalidate patents held by Prometheus Laboratories.

The decision to remand the case back to the US Court of Appeals for the Federal Circuit, which last year decided that patents Myriad has licensed and used related to the isolated gene sequences in the BRCA 1 and BRCA2 genes are valid, means that the Prometheus decision could influence or impact the case, though the effect of that case is unclear, as it centerd on different types of claims than the Myriad litigation.

The case against Myriad was brought by the Public Patent Foundation, American Civil Liberties Union, the Association for Molecular Pathology, and others who filed the suit in 2009 claiming that patents cannot cover natural phenomena and that Myriad's patents, and others like them, will hinder genetics research and keep some people from receiving the personalized medicine tests and second opinions.

Myriad has held that its patents have not hindered science, that is has not impeded research, that the pricing of its BRACAnalysis tests are not prohibitive, and that most insurers cover them. Additionally, the company also says that there are other options for people seeking second opinions.

Those assertions may not mean much if the Supreme Court at some point decides that isolated DNA is not patentable, but the CAFC in its ruling in August 2011 decided that Myriad's patents covering isolated DNA are eligible under Section 101 of the US Patent Act.

That decision in part overturned an earlier ruling from the Federal District Court for the Southern District of New York, which decided that isolated DNA was not much different from gene sequences found in nature and therefore is not patentable.

"While, this case should not have any direct impact to Myriad and its operations because of our extensive patent estate, it has great importance to the medical, pharmaceutical, biotechnology and other commercial industries, as well as the hundreds of millions of people whose lives are bettered by the products these industries develop based on the promise of strong patent protection," Myriad Genetics President and CEO Peter Meldrum said today in a statement.

"Thus, we are prepared to vigorously defend the patent claims granted to Myriad by the U.S. Patent and Trademark Office and believe that we will be successful," he said.

The plaintiffs, led by ACLU and PUBPAT, have suggested that the Prometheus decision could impact the CAFC's second look at the Myriad case, and are holding to their core argument about the special status of genes in the natural world.

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Supreme Court Bounces Myriad BRCA Gene Patent Case Back to Appeals Court for Review

The Myriad case has been closely watched by the biotechnology industry, with some insiders suggesting that a ruling against gene patenting could have a devastating effect on future innovation.

The Supreme Court ruled last week in a separate case involving medical diagnostics that companies cannot patent observations about a natural phenomenon. On Monday, it asked the lower court to revisit the Myriad case to view how it may or may not relate to that decision.

The move is expected to delay a verdict in the Myriad case by as much as several years. In the case of the individual company, that may give it enough time to benefit from the use of its contested patents. Shares in Myriad rose over 3 percent.

"Our intellectual property consultant could potentially see a scenario where the case doesn't move its way back to the Supreme Court for another 2 to 3 plus years, keeping the BRACAnalysis franchise safe from competition," said Junaid Husain, a research analyst for Dougherty & Co.

Women who test positive using Myriad's gene test, called BRACAnalysis, have an 82 percent higher risk of developing breast cancer and a 44 percent higher risk of ovarian cancer in their lifetimes. Such tests could help determine a future course of therapy.

The appeals court by a 2-1 vote had ruled the genes isolated by the company could be patented because Myriad is testing for distinctive chemical forms of the genes, and not as they appear naturally in the body. The dissenting judge said the genes could not be patented just because they were isolated from the body.

The patents granted to Myriad give the company the exclusive right to perform the genetic tests. The appeals court in its ruling in July also found that Myriad's method for screening potential therapies can be patented.

The appeals court had overturned a ruling by a federal judge in New York that the genes could not be patented.

HOW BIG A HURDLE?

Michael Yee, biotech analyst for RBC Capital Markets, said the Supreme Court not taking up the case on Monday was positive for the biotechnology industry.

Link:
Supreme Court throws out human gene patents

Public release date: 25-Mar-2012 [ | E-mail | Share ]

Contact: Marjorie Montemayor-Quellenberg mmontemayor-quellenberg@partners.org 617-534-2208 Brigham and Women's Hospital

BOSTON, MAHuman geneticists have long debated whether the genetic risk of the most common medical conditions derive from many rare mutations, each conferring a high degree of risk in different people, or common differences throughout the genome that modestly influence risk.

A new study by Brigham and Women's Hospital (BWH) researchers has harnessed data and new analysis tools to address this question in four common diseases: rheumatoid arthritis; celiac disease; coronary artery disease and myocardial infarction (heart attack); and type 2 diabetes.

The study will be electronically published on March 25, 2012 in Nature Genetics.

The researchers developed a new statistical method built upon "polygenic risk score analysis" to estimate the heritable component of these diseases that is explained by common differences throughout the genome.

Their method takes advantage of data from previously published genome-wide association studies, or GWAS, an approach used to scan DNA samples for common genetic markers seen throughout the populationcalled SNPs (single nucleotide polymorphisms).

According to senior author Robert Plenge, MD, PhD, BWH director of Genetics and Genomics in the Division of Rheumatology, Immunology and Allergy, "We used GWAS data and a Bayesian statistical framework to demonstrate that a substantial amount of risk to these four common diseases is due to hundreds of loci that harbor common causal variants with small effect, as well as a smaller number of loci that harbor rare causal variants."

Using data on rheumatoid arthritis, they estimated that variation in hundreds of locations throughout the genome might explain 20 percent of rheumatoid arthritis risk, after excluding all of the known rheumatoid arthritis genetic risk factors.

They used computer simulations to demonstrate that the underlying genetic risk in rheumatoid arthritis is largely explained by many common alleles rather than rare mutations.

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A hidden architecture: Researchers use novel methods to uncover gene mutations for common diseases

Newswise TAMPA, Fla. (March 23, 2012) An international group of researchers, including those from Moffitt Cancer Center in Tampa, Fla., have published a paper in the March 14 issue of the New England Journal of Medicine reviewing the results of a study that analyzed mutations in 18 genes of 398 patients who had acute myeloid leukemia (AML). They found that several mutated genes predicted improved outcomes when patients with certain gene mutations were given high-dose induction chemotherapy. Their findings suggest that mutational profiling could potentially be used for both risk stratification and also in helping health care providers make therapeutic decisions for some AML patients.

Previous studies have found that AML is a highly heterogenic disorder, said study co-author Hugo F. Fernandez, a senior member at Moffitt and associate chief of Moffitts Blood and Marrow Transplantation Division. Moreover, recent studies have revealed that a number of genetic mutations in AML patients might have prognostic value. The question of the presence of these gene mutations altering outcomes based on current therapy had not been answered to date.

Their paper cites a clinical trial carried out by the Eastern Cooperative Oncology Group (ECOG) in which dose-intensified chemotherapy improved outcomes in two age sets of AML patients. Based on these findings, the research team hypothesized that carrying out mutational analysis of all known molecular alterations occurring in more than 5 percent of patients with AML might allow for the identification of distinct, molecularly defined subgroups of patients who might benefit from dose-intensified chemotherapy.

The laboratory research team subsequently performed a mutational analysis on diagnostic samples from 398 patients enrolled in the ECOG clinical trial they cited and used patients frozen sample cells for extraction and profiling. The researchers validated the results of this latter group of 104 patients.

We found that intensification of the dose of anthracycline significantly improved outcomes and overall survival in patients with mutations in DNMT3A, NPM1 or MLL translocations, said Fernandez. This finding suggests that mutational profiling could be used to determine which AML patients will benefit from dose-intensive induction therapy.

Most importantly, said Fernandez, this study demonstrates how integrated mutational profiling of samples from a clinical trial cohort can advance understanding of the biologic characteristics of AML.

About Moffitt Cancer Center Follow Moffitt on Facebook: http://www.facebook.com/MoffittCancerCenter Follow Moffitt on Twitter: @MoffittNews Follow Moffitt on YouTube: MoffittNews

Located in Tampa, Moffitt Cancer Center is a National Cancer Institute-designated Comprehensive Cancer Center, which recognizes Moffitts excellence in research and contributions to clinical trials, prevention and cancer control. Moffitt is also a member of the National Comprehensive Cancer Network, a prestigious alliance of the countrys leading cancer centers, and is listed in U.S. News & World Report as one of Americas Best Hospitals for cancer.

Media release by Florida Science Communications

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Identifying Acute Myeloid Leukemia Gene Mutations May Indicate Risk, Best Treatment

Editor's Choice Academic Journal Main Category: Genetics Also Included In: Neurology / Neuroscience Article Date: 22 Mar 2012 - 6:00 PDT

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During an examination of various mutant fruit flies for defects leading to progressive degeneration of photoreceptors in the flies' eye, Vafa Bayat, a recent graduate from the Program in Developmental Biology at BCM and his team discovered mutations in the fruit fly gene that encode a mitochondrial enzyme called the mitochondrial methionyl-tRNA synthetase (Aats-met) that decreases life span and causes other problems, such as lower cell proliferation.

Mitochondria are sometimes described as "cellular power plants", due to the fact that they produce most of the cell's supply of adenosine triphosphate (ATP), which is used as a source of chemical energy. However, they are also involved in processes, such as signaling, cellular differentiation, cell death and regulating cell cycles and cell growth.

Defective genes that encode mitochondrial proteins are also known to implicate human metabolic and neurological disorders.

Dr. Bayat, and his team checked medical literature for genetic neurological disorders, which scientists thought were caused by defects in the region of the genome that contains the human version of the Aats-met gene, MARS2.

Dr. Bernard Brais and team had already mapped one such disease to this region of the genome, i.e. Autosomal Recessive Spastic Ataxia with frequent Leukoencephalopathy (ARSAL). However they failed to identify the precise gene responsible. Ataxias, like ARSAL, are progressive neurodegenerative diseases, which amongst other problems cause coordination difficulties that result in modified gait and speech.

The Montreal team, led by Dr. Isabelle Thiffault, discovered that in ARSAL patients the genetic material of the MARS2 gene is comprehensively rearranged, which resulted in reduced levels of the MARS2 enzyme, reduced synthesis of proteins by the mitochondria, and impaired mitochondrial function. Similar to the fruit fly mutants, the patients' cells also displayed higher levels of reactive oxygen species that can cause damage to cells and their genetic material, as well as slow cell proliferation.

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Neurodegenerative Disorders In Humans And Fruit Flies Caused By Same Gene Mutations

ScienceDaily (Mar. 21, 2012) Healthy individuals who carry a gene variation linked to an increased risk of autism have structural differences in their brains that may help explain how the gene affects brain function and increases vulnerability for autism. The results of this innovative brain imaging study are described in an article in the groundbreaking neuroscience journal Brain Connectivity, a bimonthly peer-reviewed publication from Mary Ann Liebert, Inc. The article is available free online at the Brain Connectivity website.

"This is one of the first papers demonstrating a linkage between a particular gene variant and changes in brain structure and connectivity in carriers of that gene," says Christopher Pawela, PhD, Co-Editor-in-Chief and Assistant Professor, Medical College of Wisconsin. "This work could lead to the creation of an exciting new line of research investigating the impact of genetics on communication between brain regions."

Although carriers of the common gene variant CNTNAP2 -- identified as an autism risk gene -- may not develop autism, there is evidence of differences in brain structure that may affect connections and signaling between brain regions. These disruptions in brain connectivity can give rise to functional abnormalities characteristic of neuropsychological disorders such as autism.

Emily Dennis and coauthors from UCLA School of Medicine and UCLA (Los Angeles, CA) and University of Queensland and Queensland Institute of Medical Research (Brisbane, Australia), used a sophisticated imaging technique to study the brains of healthy young adults who are carriers of CNTNAP2.

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The above story is reprinted from materials provided by Mary Ann Liebert, Inc./Genetic Engineering News.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Autism risk gene linked to differences in brain structure

Genetic studies find dysregulation in pathways that govern development of the prefrontal cortex in young patients with autism

Newswise A study led by Eric Courchesne, PhD, director of the Autism Center of Excellence at the University of California, San Diego School of Medicine has, for the first time, identified in young autism patients genetic mechanisms involved in abnormal early brain development and overgrowth that occurs in the disorder. The findings suggest novel genetic and molecular targets that could lead to discoveries of new prevention strategies and treatment for the disorder.

The study to be published on March 22 in PLoS Genetics uncovered differences in gene expression between brain tissue from young (2 to14 years old) and adult individuals with autism syndrome disorder, providing important clues why brain growth and development is abnormal in this disorder.

Courchesne first identified the link between early brain overgrowth and autism in a landmark study published by the Journal of the American Medical Association (JAMA) in 2003. Next, he tested the possibility that brain overgrowth might result from an abnormal excess of brain cells. In November 2011, his study, also published in JAMA, discovered a 67 percent excess of brain cells in a major region of the brain, the prefrontal cortex a part of the brain associated with social, communication and cognitive development.

Our next step was to see whether there might be abnormalities of genetic functioning in that same region that might give us insight into why there are too many cells and why that specific region does not develop normally in autism, said Courchesne.

In the new study, the researchers looked towards genes for answers, and showed that genetic mechanisms that normally regulate the number of cortical neurons are abnormal. The genes that control the number of brain cells did not have the normal functional expression, and the level of gene expression that governs the pattern of neural organization across the prefrontal cortex is turned down. There are abnormal numbers and patterns of brain cells, and subsequently the pattern is disturbed, Courchesne said. This probably leads to too many brain cells in some locations, such as prefrontal cortex, but perhaps too few in other regions of cortex as well.

In addition, the scientists discovered a turning down of the genetic mechanisms responsible for detecting DNA defects and correcting or removing affected cells during periods of rapid prenatal development.

Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings in the brain at young ages have remained largely unknown. Until now, few studies have been able to investigate whole-genome gene expression and genotype variation in the brains of young patients with autism, especially in regions such as the prefrontal cortex that display the greatest growth abnormality.

Scientists including co-first authors Maggie Chow, PhD, and Tiziano Pramparo, PhD, at UC San Diego identified abnormal brain gene expression patterns using whole-genome analysis of mRNA levels and copy number variations from 33 autistic and control postmortem brain samples. They found evidence of dysregulation in the pathways that govern cell number, cortical patterning and cell differentiation in the young autistic prefrontal cortex. In contrast, in adult patients with autism, the study found that this area of the brain shows dysregulation of signaling and repair pathways.

Our results indicate that gene expression abnormalities change across the lifespan in autism, and that dysregulated processes in the developing brain of autistic patients differ from those detected at adult ages, said Courchesne. The dysregulated genetic pathways we found at young ages in autism may underlie the excess of neurons and early brain overgrowth associated with this disorder.

Excerpt from:
Gene Expression Abnormalities in Autism Identified

Public release date: 20-Mar-2012 [ | E-mail | Share ]

Contact: Bryan Ghosh bghosh@plos.org 44-122-344-2837 Public Library of Science

A collaborative study by scientists at Baylor College of Medicine (BCM) and the Montreal Neurological Institute of McGill University, and published March 20 in the online, open access journal PLoS Biology, has discovered that mutations in the same gene that encodes part of the vital machinery of the mitochondrion can cause neurodegenerative disorders in both fruit flies and humans.

Vafa Bayat in Dr. Hugo Bellen's lab at BCM, examined a series of mutant fruit flies for defects leading to progressive degeneration of photoreceptors in the eye. They identified mutations in the fruit fly gene that encodes a mitochondrial enzyme known as the mitochondrial methionyl-tRNA synthetase (Aats-met). These mutations also shortened life span and caused other problems, including reduced cell proliferation.

Mitochondria are the power plants of the cell, and have their own mechanism for producing proteins, separate from the main cellular protein-producing machinery. Defects in genes that encode mitochondrial proteins have been previously associated with human metabolic and neurological disorders.

Dr. Bayat, a recent graduate from the Program in Developmental Biology at BCM, searched the medical literature for genetic neurological disorders that were thought to be caused by defects in the region of our genome that contains the human version of the Aats-met gene, MARS2. One such disease, Autosomal Recessive Spastic Ataxia with frequent Leukoencephalopathy (ARSAL), had already been mapped to this region of the genome by Dr. Bernard Brais and his colleagues, but the precise gene responsible was not known. Ataxias such as ARSAL are progressive neurodegenerative diseases that cause coordination problems, leading to modified gait and speech as well as other problems.

Dr. Isabelle Thiffault from the Montreal team identified complex rearrangements of the genetic material in the MARS2 gene of ARSAL patients. These unusual rearrangements resulted in reduced levels of the MARS2 enzyme, reduced synthesis of proteins by the mitochondria, and impaired mitochondrial function. As with the fruit fly mutants, the patients' cells also had increased levels of reactive oxygen species, which can damage cells and their genetic material, and slow cell proliferation.

"We found the same defect in the mitochondrial respiratory chains in the human cells, which produced a lot of reactive oxygen species," said Dr. Bayat. "When we feed the fly larvae antioxidants, they suppress the degenerative phenotypes in flies." The ability of antioxidants to counteract the negative consequences of the mutant gene in flies raises the possibility that a related approach might have beneficial effects in human patients, though this remains to be determined.

"While the discovery of mutations in fly genes has been linked to human disease before, it has often taken many years to decades to accomplish this," said Dr. Bellen. "This was a relatively quick process. In summary, we have shown that you can use flies to identify fly mutants with neurodegenerative phenotypes and that these mutants can assist in the identification of human disease genes."

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Link:
Collaboration rapidly connects fly gene discovery to human disease

01-03-2012 10:59 http://www.globalchange.com Future health trends -- how to predict future health by genetic prophecy. Matching your genes to medical history of others in the general population who may differ in age, gender, location, wealth, culture, but who may share vital indicators of future disease. Impact of gene profiling and pharmacogenomics on health care, from chosing the right medication to treat illness and disease, avoiding serious side effects, matching personal profile to treatment plans. Also gene profiling as part of health promotion, disease prevention, wellness and performance-based medicine. Enhancing performance -- whether sexual performance, mental performance (students or older people with Alzheimer's disease memory impairment / loss). Impact of ageing and obesity on consumer health spending, government budgets, health care, workforce and retirement age. Futurist conference keynote speaker Patrick Dixon -- speaking at corporate event for Novo Nordisk.

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How to Predict Sickness: gene prophecy - future of pharmaceutical industry, health keynote speaker - Video

But if youre listening to one person sing, and he changes his tempo, youre still going to stay in tune with him, said Meni Wanunu, an assistant professor of physics in Northeasterns College of Science.

Wanunu used the analogy to explain the difference between older and newer gene sequencing techniques. Old techniques, he said, analyzed millions of DNA molecules at a time. But new techniques take a single-molecule approach, a strategy that has the potential to revolutionize the field once a few significant challenges are overcome.

By obtaining the sequence of an organisms genetic material with ease, scientists can explore a range of research areas, from correlating genes with functions to answering evolutionary mysteries. Doctors can use gene sequencing to test for specific genes that are related to specific diseases, such as breast and ovarian cancers. Patients could learn in their home what foods to avoid and which drugs would be most effective for them.

Older and current commercial sequencing technologies are too expensive for realizing personalized health and medicine applications. By studying DNA motion through nanopores, Wanunus team and others in the field hope to provide simple and straightforward approaches that could reduce sequencing costs by a thousand times, making it available for all.

In an article published on Sunday in the journal Nature Methods, Wanunu and colleagues at University of Pennsylvania and Columbia University unveiled a device that speeds up the rate at which DNA molecules can be detected, a significant step toward reading their sequence.

Wanunu, who joined the Northeastern faculty in September, designs nanoscale membranes that contain pores through which charged particles, such as DNA molecules and salt ions, can pass when exposed to an electric field.

When a long DNA molecule passes through a pore, the membranes current momentarily subsides, yielding a negative spike in voltage signal. DNA consists of many repeating subunits called bases, each of which has previously been shown to exhibit a characteristic signal spike.

Existing state-of-the-art techniques cant measure current changes though a nanopore fast enough to allow reading each base. You can show that DNA was there, but not what the sequence is, Wanunu explained.

Slowing down DNA movement by lowering the voltage is not a practical solution, Wanunu said. If you lower the voltage too much, at some point DNA will not want to enter and if it doesnt enter you wont be able to read it. If it enters too fast, youre not going to know the sequence.

Armed with this information, the team focused their efforts on speeding up the rate of measurement. By thinking outside the box (literally), Wanunu's colleagues Jacob Rosenstein and Ken Shepard from Columbia University designed a miniature "patch-clamp amplifier" that is 10 times smaller than traditional amplifiers. More importantly, it is 10 times faster, being able to read current through the nanopore about every half microsecond just about the time it takes for a DNA base to move through.

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Gene sequencing at warp speed

A single gene's effect on the brain can result in non-stop eating, research has shown.

Scientists believe the "gluttony gene" may be responsible for cases of obesity caused by out-of-control appetite.

The Bdnf gene variant was studied in mice. It was found to prevent brain neurons from transmitting signals that tell the body it has eaten enough.

"This discovery may open up novel strategies to help the brain control body weight," said lead researcher Dr Baoki Xu, from Georgetown University Medical Centre in the US.

Hunger and satiety, the sensation of "feeling full", are governed by a complex balance of hormonal and neuronal signals.

Two hormones in particular, leptin and insulin, released in the body after a meal play a key role.

Their chemical signals activate neurons in the hypothalamus region of the brain that trigger satiety. But if the connection is not made, the craving for food continues.

"Short" versions of the Bdnf gene block the leptin and insulin signals and prevent the "stop eating" message passing through the brain to the correct appetite-suppressing locations, say the scientists.

The research is reported online in the journal Nature Medicine.

Bdnf makes a protein that is synthesised in dendrites, the branch-like "fingers" that project from nerve cells. Dendrites carry the synapses that neurons use to communicate to each other.

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'Gluttony gene’ may be behind big appetites

SCIENTISTS here have found a mutation in a gene that makes some cancer drugs less effective, as well as a solution to tackle this problem.

This mutation appears in about 15% of East Asians, and to a lesser extent in other Asians, but is completely absent in Caucasians and Africans.

A team of 55 researchers, led by Assoc Prof Ong Sin Tiong of Duke-NUS Graduate Medical School, found that targeted drugs to combat specific types of lung and blood cancers did not work as well in patients with the mutated gene.

However, the shortcoming can be addressed by the addition of another drug that is currently not commercially available, but is used in clinical trials elsewhere.

The existing targeted drugs, which block the growth and spread of the cancer by interfering with the molecules that cause the tumour to grow, are not cheap.

The bill can come up to S$2,000 (RM4,800) to S$3,000 (RM7,200) a month for lung cancer patients, with the drug able to extend life by as much as 30 months.

For leukaemia, the cost is S$4,000 (RM9,600) to S$5,000 (RM12,000) a month, with patients living a good-quality life for as long as a decade.

However, in about 20% of patients with these forms of cancers, the drug benefit is not as good as it is for the rest.

The teams findings have been published in Nature Medicine considered one of the the worlds top biomedical journals.

Prof Patrick Casey, senior vice-dean for research at Duke-NUS Graduate Medical School, called the discovery spectacular.

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Gene mutation found

A single gene's effect on the brain can result in non-stop eating, research has shown.

Scientists believe the "gluttony gene" may be responsible for cases of obesity caused by out-of-control appetite.

The Bdnf gene variant was studied in mice. It was found to prevent brain neurons from transmitting signals that tell the body it has eaten enough.

"This discovery may open up novel strategies to help the brain control body weight," said lead researcher Dr Baoki Xu, from Georgetown University Medical Centre in the United States.

Hunger and satiety, the sensation of "feeling full", are governed by a complex balance of hormonal and neuronal signals.

Two hormones in particular, leptin and insulin, released in the body after a meal play a key role.

Their chemical signals activate neurons in the hypothalamus region of the brain that trigger satiety. But if the connection is not made, the craving for food continues.

"Short" versions of the Bdnf gene block the leptin and insulin signals and prevent the "stop eating" message passing through the brain to the correct appetite-suppressing locations, say the scientists.

The research is reported in the journal Nature Medicine.

Bdnf makes a protein that is synthesised in dendrites, the branch-like "fingers" that project from nerve cells. Dendrites carry the synapses that neurons use to communicate to each other.

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'Gluttony gene' may explain out-of-control appetite

London, March 19 (ANI): Researchers have revealed how a mutation in a single gene is responsible for the inability of neurons to effectively pass along appetite suppressing signals from the body to the right place in the brain, which results in obesity caused by a voracious appetite.

Researchers at Georgetown University Medical Center suggested there might be a way to stimulate expression of that gene to treat obesity caused by uncontrolled eating.

The research team specifically found that a mutation in the brain-derived neurotrophic factor (Bdnf) gene in mice does not allow brain neurons to effectively pass leptin and insulin chemical signals through the brain.

In humans, these hormones, which are released in the body after a person eats, are designed to "tell" the body to stop eating. But if the signals fail to reach correct locations in the hypothalamus, the area in the brain that signals satiety, eating continues.

"This is the first time protein synthesis in dendrites, tree-like extensions of neurons, has been found to be critical for control of weight," said the study's senior investigator, Baoji Xu, Ph.D., an associate professor of pharmacology and physiology at Georgetown.

"This discovery may open up novel strategies to help the brain control body weight," he noted.

Xu has long investigated the Bdnf gene. He has found that the gene produces a growth factor that controls communication between neurons.

For example, he has shown that during development, BDNF is important to the formation and maturation of synapses, the structures that permit neurons to send chemical signals between them.

The Bdnf gene generates one short transcript and one long transcript. He discovered that when the long-form Bdnf transcript is absent, the growth factor BDNF is only synthesized in the cell body of a neuron but not in its dendrites. The neuron then produces too many immature synapses, resulting in deficits in learning and memory in mice.

Xu also found that the mice with the same Bdnf mutation grew to be severely obese.

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Gluttony gene that makes you eat more even when you are full identified

London, March 19 (ANI): Scientists have now found answer to why some patients fail to respond to some of the most successful cancer drugs.

Tyrosine kinase inhibitor drugs (TKIs) work effectively in most patients to fight certain blood cell cancers, such as chronic myelogenous leukemia (CML), and non-small-cell lung cancers (NSCLC) with mutations in the EGFR gene.

These precisely targeted drugs shut down molecular pathways that keep these cancers flourishing and include TKIs for treating CML, and the form of NSCLC with EGFR genetic mutations.

Now, a multi-national research team led by scientists at Duke-NUS Graduate Medical School in Singapore, working with the Genome Institute of Singapore (GIS), Singapore General Hospital and the National Cancer Centre Singapore, has discovered that there is a common variation in the BIM gene in people of East Asian descent that contributes to some patients' failure to benefit from these tyrosine kinase inhibitor drugs.

"Because we could determine in cells how the BIM gene variant caused TKI resistance, we were able to devise a strategy to overcome it," said S. Tiong Ong, M.B.B. Ch., senior author of the study and associate professor in the Cancer and Stem Cell Biology Signature Research Programme at Duke-NUS and Division of Medical Oncology, Department of Medicine, at Duke University Medical Center.

"A novel class of drugs called the BH3-mimetics provided the answer," he said.

"When the BH3 drugs were added to the TKI therapy in experiments conducted on cancer cells with the BIM gene variant, we were able to overcome the resistance conferred by the gene. Our next step will be to bring this to clinical trials with patients," Ong added.

Yijun Ruan, Ph.D., a co-senior author of this study and associate director for Genome Technology and Biology at GIS said: "We used a genome-wide sequencing approach to specifically look for structural changes in the DNA of patient samples. This helped in the discovery of the East Asian BIM gene variant. What's more gratifying is that this collaboration validates the use of basic genomic technology to make clinically important discoveries."

If the drug combination does override TKI resistance in people, this will be good news for those with the BIM gene variant, which occurs in about 15 percent of the typical East Asian population. By contrast, no people of European or African ancestry were found to have this gene variant.

"While it's interesting to learn about this ethnic difference for the mutation, the greater significance of the finding is that the same principle may apply for other populations," said Patrick Casey, Ph.D., senior vice dean for research at Duke-NUS and James B. Duke Professor of Pharmacology and Cancer Biology.

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Gene variant in East Asians could explain resistance to cancer drugs

London, March 19 (IANS) Scientists have stumbled on a 'gluttony gene' that converts you into an eating machine even if you are full.

Mice tests have demonstrated that a mutation on a single gene broke down body-brain communication and triggered non-stop eating and rapid weight gain.

But the good news is that the scientists hope identifying the Bdnf gene could help with slimming treatments as obesity is becoming a global epidemic, the journal Nature Medicine reports.

Baoki Xu, who led the study at Georgetown University Medical Centre, US on variations in the Bdnf gene in mice, said: "This discovery may open up novel strategies to help the brain control body weight."

His team found the Bdnf gene has 'short' and 'long' versions which form at an early stage in the womb. Those with the 'long' form sent the chemical signals to say 'I'm full' through a 'superhighway' of neurons in the brain to the hypothalamus, according to the Daily Mail.

In those with the short form, signals reached some brain cells but could not be picked up by the dendrites - the branch-like 'fingers' coming out of the cells which pass messages on to the right place.

Xu said: "If there is a problem with the Bdnf gene, neurons can't talk to each other, and the leptin and insulin signals are ineffective and the appetite is not modified." The mice ate twice as much as those without the mutation.

Humans also have this gene and it has been linked to obesity, but the researchers say it was not clear until now exactly how it worked.

After a meal, the activity of this gene transmits chemical signals down a chain of brain cells until they reach the hypothalamus, which receives the message that you are full and suppresses the appetite.

Scientists will now be looking at whether the faulty transmission line can be modified, to help prevent and treat obesity.

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'Gluttony gene' forces you to gobble non-stop

ScienceDaily (Mar. 18, 2012) Researchers at Georgetown University Medical Center have revealed how a mutation in a single gene is responsible for the inability of neurons to effectively pass along appetite suppressing signals from the body to the right place in the brain. What results is obesity caused by a voracious appetite.

Their study, published March 18th on Nature Medicine's website, suggests there might be a way to stimulate expression of that gene to treat obesity caused by uncontrolled eating.

The research team specifically found that a mutation in the brain-derived neurotrophic factor (Bdnf) gene in mice does not allow brain neurons to effectively pass leptin and insulin chemical signals through the brain. In humans, these hormones, which are released in the body after a person eats, are designed to "tell" the body to stop eating. But if the signals fail to reach correct locations in the hypothalamus, the area in the brain that signals satiety, eating continues.

"This is the first time protein synthesis in dendrites, tree-like extensions of neurons, has been found to be critical for control of weight," says the study's senior investigator, Baoji Xu, Ph.D., an associate professor of pharmacology and physiology at Georgetown.

"This discovery may open up novel strategies to help the brain control body weight," he says.

Xu has long investigated the Bdnf gene. He has found that the gene produces a growth factor that controls communication between neurons.

For example, he has shown that during development, BDNF is important to the formation and maturation of synapses, the structures that permit neurons to send chemical signals between them. The Bdnf gene generates one short transcript and one long transcript. He discovered that when the long-form Bdnf transcript is absent, the growth factor BDNF is only synthesized in the cell body of a neuron but not in its dendrites. The neuron then produces too many immature synapses, resulting in deficits in learning and memory in mice.

Xu also found that the mice with the same Bdnf mutation grew to be severely obese.

Other researchers began to look at the Bdnf gene in humans, and large-scale genome-wide association studies showed Bdnf gene variants are, in fact, linked to obesity.

But, until this study, no one has been able to describe exactly how BDNF controls body weight.

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How a single gene mutation leads to uncontrolled obesity

Editor's Choice Academic Journal Main Category: Obesity / Weight Loss / Fitness Also Included In: Genetics;Neurology / Neuroscience Article Date: 19 Mar 2012 - 11:00 PDT

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The researchers found that the mutation in the Bdnf (brain-derived neurotrophic factor) gene undermines brain neurons' ability to pass insulin and leptin chemical signals through the brain. Their study involved mice.

When a human being has eaten, leptin and insulin are released into the body and literally tell the body to stop consuming food. However, if the signals do not reach parts of the brain they are supposed to - within the hypothalamus - the person will continue feeling hungry, and will carry on eating.

Baoji Xu, Ph.D., said:

Dr. Xu has been carrying out research on the Bdnf gene for years. He explains that this gene produces a growth factor that regulates how neurons communicate with each other.

Xu has demonstrated that during development, BDNF plays a major role in the formation and maturity of synapses. A synapse is the point where two nerve cells connect; a specialized junction at which a neuron (nerve cell) communicates with a target cell - this is done via chemical signals. The Bdnf gene produces one short and one long transcript. When the long-form BdnfN transcript is not there, the growth factor BDNF is only produced in the body of the neuron, but not in its dendrites. This results in the production of too many immature synapses, which undermines learning and memory in mice.

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Gene Mutation Causes Uncontrolled Obesity

Could lead to treatments for obesity

By Tamara Cohen

PUBLISHED: 14:28 EST, 18 March 2012 | UPDATED: 14:28 EST, 18 March 2012

The secret to staying slim may be all in your genes.

Scientists believe they have found the gluttony gene which fails to tell your brain when you are full.

In tests on mice, they showed that a mutation on a single gene broke down communication in the body and led to non-stop eating and rapid weight gain.

Gut buster: Scientists believe they have uncovered a gene which makes you eat even when are full because it breaks down communication between the body and the brain

But the good news is, they hope identifying the gene could help with treatments for obesity which affects nearly one in four adults in the UK.

Researchers at Georgetown University Medical Centre in the U.S. studied variations in the Bdnf gene in mice.

The rest is here:
Georgetown University Medical Centre: Scientists discover 'greedy gene¿ that makes you eat more even when you are full