Autoimmunity, Brain & Beyond

This from the Lupus Research Institute....

A “Breakthrough Decade”: $100 Million for Innovative Lupus Research

It was announced last night that over the past decade, the Lupus Research Institute (LRI)’s pioneering science has generated $100 million in new research funding for the devastating autoimmune disease of systemic lupus.

“In powering unprecedented scientific discovery, the LRI has forever changed the field of lupus research,” said LRI Board Member Richard K. DeScherer at the annual S.L.E. Lupus Foundation gala in New York. “LRI scientists have turned $30 million dollars in initial LRI grant funding into $70 million more from the National Institutes of Health (NIH).

“That’s what we call a breakthrough decade!” he said. “An incredible $100 million dollars for entirely new science in lupus—innovative work that would not exist without the LRI taking risks on the most brilliant scientific minds in the country.”

“The LRI strategy of funding novel scientific ideas in lupus has more than demonstrated its power,” said William E. Paul, MD, chief of the Laboratory of Immunology at NIAID-NIH, and chair of the LRI Scientific Advisory Board. “The LRI model strengthens the lupus research landscape by moving novel concepts forward to secure large-scale federal funding.”

“The speed with which the Institute has changed the outlook for lupus research is remarkable,” Dr. Paul said. 

The LRI selects Novel Research Grant awards based on creativity, novelty, and potential to drive scientific discovery. To date, the Institute has awarded $30 million to 108 investigators at 55 academic medical centers across 22 states.

More than 65 percent of LRI-funded researchers have gone on to win extended funding from the NIH to further pursue their work, including:

• Betty Diamond, MD, at the Feinstein Institute for Medical Research (North Shore-LIJ Health System) in New York. The LRI funded Dr. Diamond’s initial work on the role of stress hormones in allowing toxic antibodies to penetrate the brain in lupus and destroy nerve cells there, causing memory loss, confusion, and other cognitive problems. She went on to receive an NIH program grant for $6.5 million to build on strategies to deal with this devastating development.

• Marcus Clark, MD, at the University of Chicago. With LRI funding, Dr. Clark showed that the kidneys of people with lupus actually contain the activated B cells that directly promote inflammation and damage in these critical organs. The NIH provided an additional $1.7 million to further explain and expand on this major discovery. “This government grant was funded based entirely on research supported by the LRI,” Dr. Clark said.

• Greg E. Lemke, PhD, at La Jolla, California’s Salk Institute for Biologic Studies. Dr. Lemke proposed the novel idea that a curious family of “TAM” receptors might function as a core ‘control switch’ over the immune system’s inflammatory response. He received an additional $1.4 million from the NIH and others to explore exciting new approaches to shutting down the uncontrolled inflammation of lupus by restoring immune system regulation. “Without the LRI, this project would have stopped—and a fundamental discovery in immunology would not have happened,” Dr. Lemke said.

“What an incredible investment the LRI has been,” said LRI Co-Chairman Robert J. Ravitz. “It has paid off in a decade of stellar return on results that matter for people with lupus, and my wife and I now have such hope that our daughter Annie and millions of others will soon have answers on how to stop lupus.”

LRI President Margaret G. Dowd added, “We are very grateful to our supporters for believing and investing in LRI’s powerful research model for breakthroughs in lupus. Their bold commitment is enabling innovative science to successfully blaze the path to a cure and a hope-filled new decade for people with this devastating disease.”

 

New and cool web site...

Every now and then I happen on to a nice web site and wanted to share it http://www.disease.com/

The Lupus Research Institute (LRI) Announces 2009 Research Awards

The Lupus Research Institute (LRI) today named 12 new grant recipients for 2009. The awards, totaling $3.6 million, recognize innovative work across a broad spectrum of lupus research. Anne Davidson, MD, a lupus researcher at The Feinstein Institute for Medical Research, was one of this year's recipients. To read more about Dr. Davidson's research grant go to:

http://lupusresearchinstitute.org/research/grant_recipients/davidson/anne

Epilepsy Medicine Tested to Treat Cocaine Addiction

They were Mexican parolees with an addiction to cocaine. They were also desperate pioneers whose drug use had gotten the better of them every day for years. They signed on to a double-blind, placebo-controlled study to test whether an epilepsy drug could reduce their use of cocaine. In the end, 14 of the 50 parolees who were taking a medicine called vigabatrin spent the final three weeks of the study with no signs of cocaine use on twice weekly urine tests, compared to four of 53 who swallowed a placebo dose. They were also less likely to be drinking alcohol during this same time period.

    The study, conducted by Stephen L. Dewey, PhD of The Feinstein Institute for Medical Research in Manhasset, NY, and Jonathan D. Brodie, MD, PhD, of New York University School of Medicine and their colleagues, appears in the November issue of the American Journal of Psychiatry.

    Dr. Dewey and Dr. Brodie have spent more than a decade working on animal models, and now drug abusers, following their initial findings that the drug blocks important reinforcement regions of the brain tied to addiction. The scientists just received a $1.2 million grant from the U.S Department of Defense to continue their work in treating human addictions.

    “In animal models, vigabatrin works to reduce the use of virtually every addictive substance,” said Dr. Dewey. The work was conducted at Brookhaven National Laboratory, where Dr. Dewey had worked from 1996 until moving his laboratory to the Feinstein Institute earlier this year. It was in 1998 when he discovered that the epilepsy drug, which had been approved for use in Europe but not in the United States, showed potential to end cocaine addiction. A year later, it was used for smoking cessation and then methamphetamine. The drug was even used to see if it could reduce cravings for high-sugar, high-fat food.

    It was recently approved by the US Food and Drug Administration for use in epilepsy treatment. "If this can do for humans what it did for animals, we may have opened the door for addicts around the world to kick their habit," said Dr.  Dewey. Gamma vinyl GABA, or GVG, blocks the chemical process that triggers the "high." The substance increases the amount of the brain's most common neurotransmitter, GABA. The increased GABA allows brain cells to communicate more effectively.

    The researchers became interested in GVG because it also reduces the level of another brain chemical called dopamine. This brain substance has been shown to modulate pleasure and reward, as well as other behaviors. Cocaine users experience a "high" because the drug - and other mind-altering substances - seems to stimulate a flood of dopamine in the brain regions that govern reinforcing and rewarding behavior in humans and animals alike. Dopamine is known as the "feel-good" transmitter, although it has many different roles in the brain. Vigabatrin reduces levels of dopamine in the circuits of the brain that govern reward.

    About 30 million people in the United States have used cocaine, and about one to three million would be considered addicted, experts say. There are no medicines approved for cocaine addiction.

    The current study is the first double-blind, placebo-controlled study of the drug in addicts. The men and women who signed on to the trial arrived to the clinic as part of their parole requirements after being released from prison. They had an average daily use of two grams per day for about nine years. They agreed to be part of the study even though half of them would end up on a placebo. The medicine is a powder that they mixed with orange juice.

    At the end of three months, four times as many people taking vigabatrin completely stopped using cocaine for at least three weeks compared to those swallowing a placebo powder in their juice. They were also far more likely to report abstinence from alcohol.

    There have been concerns moving forward with this drug. One of the reasons it was not approved in the U.S. until recently was that there is a rare but troubling side effect: a narrowing of visual field. And there are indications these defects could grow more serious over time.

    Dr. Dewey and Dr. Brody teamed with a biotech company – Catalyst Pharmaceutical Partners – that has licensed the use of the drug for the treatment of cocaine addiction. They have a long way to go before vigabatrin could be used to treat addictions. They need much larger studies and must figure out how much to give and whether it could be given over a long-term period. In the current study, the only side effect was tiredness.

    Dr. Dewey’s research on the addicted brain has led him into Long Island schools to educate young people, parents and teachers on the dangers of the brain on drugs. His lectures and town hall meetings have become so popular that he was asked last month to speak to The Welfare to Work Commission of the Suffolk County Legislature during a public meeting on a growing network of “sober homes.”

Experimental Medicine Protects Against Organ Failure

Seventy-five thousand people who undergo surgery or are admitted to the Emergency Department experience a potentially life-threatening condition: A temporary loss of oxygen that can set in motion a rogue inflammatory response that can lead to multiple organ failure.

 

Ping Wang, MD, a scientist at The Feinstein Institute for Medical Research, is testing the benefits of an experimental medicine that can clear away dying cells and reduce the risk for ischemia reperfusion injury in the gut. In a study published in the American Journal of Respiratory Critical Care Medicine, Dr. Wang and his colleagues used an experimental medicine called MFG-E8 on the heels of ischemia and found that it significantly lowered the risk for reperfusion injury.  Normally, when tissue suffers from a temporary loss of oxygen the body makes an unusual response when the oxygen starts to flow again. It sets off an inflammatory response. These inflammatory cells actually target tissue and can trigger multiple organ failure. The lung is most susceptible to this type of injury, which is why in humans it can be deadly.

 

MFG-8 blocked the acute lung injury in an animal model of ischemic reperfusion. Forty-seven percent of the animals exposed to MFG-8 survived for at least 24 hours while none of placebo mice survived, according to Dr. Wang. MFG-8 is a protein normally produced by the spleen to enhance clearance of dying cells. The Feinstein scientists at Dr. Wang’s laboratory made a recombinant human protein. The idea to use the protein emerged after their studies showed that MFG-8 levels drop markedly on the heels of ischemia reperfusion. Spleen cells just can’t produce enough of the substance to clean up the dying cells. If the cells are not removed – and this cellular garbage continues to accumulate – this necrosis (or cell death) can cause acute lung injury.

 

They found that the medicine helped clear out the majority of the dying cells in the hard-hit lung. It also reduced inflammation at the site. And the most hopeful news was that about half of the animals survived the injury. The work in the laboratory will continue to address questions that need answering: Will the recombinant human protein be safe to patients? How much will be enough to protect against organ failure?

 

Right now, there is no approved effective medicine to treat intestinal ischemic reperfusion. Dr. Wang said that there are 25,000 to 50,000 deaths a year related to this intestinal injury.

Bettie Steinberg, PhD, honored in "Sixty Over Sixty" Award

Bettie Steinberg, PhD, a scientist at The Feinstein Institute for Medical Research and dean of the Elnezzi Graduate School of Molecular Medicine,  was celebrated for her outstanding acheivements in science by the non-profit organization, the School-Business Partnerships of Long Island, Inc.

The idea for the award is simple: Find 60 people over 60 who fulfilled their dreams and hope they inspire younger people to do the same.

Dr. Steinberg is an expert in human papillomavirus and has identified novel experimental treatments to block respiratory papillomas that are now in clinical trials.

Congratulations, Bettie.

New Department of Defense Grant to study Traumatic Brain Injury

Dr. Rongqian Wu of The Feinstein Institute for Medical Research has received a coveted award from the Department of Defense to study experimental treatments for Traumatic Brain Injury. Dr. Wu was one of twenty‐eight (28) recipients (out of 453 applicants) for the Deployment Related Medical Research Program Hypothesis Development Award. Dr. Wu will be studying the use of Ghrelin for the treatment of Traumatic Brain Injury (TBI) and the brain bleeds. Ghrelin is a hormone best known for its regulation in eating behavior and fat regulation but there is growing evidence that it has anti-inflammatory effects.

 

The award is designed to support to protect, support, and advance the research projects tailored to address problems in the military milieu across field, shipboard, garrison, primary care, behavioral health care, or combat settings. The DRMRP challenged the scientific and clinical communities to develop innovative ideas that will leapfrog the delivery of emerging new approaches, technologies, and agents to the military through basic science, translational, and/or clinical research.

 

The DRMRP sought deployment‐related proposals in clinical, cognitive/behavioral, computational, epidemiologic, laboratory and field research, as well as public health and policy, international health and humanitarian relief, environmental sciences related to optimal healing, nursing, occupational health, complementary and alternative therapies, ethics, medical safety, and economics. Interdisciplinary and integrative health approaches are encouraged.

 

This is the first funding year of the DRMRP Hypothesis Development Award. Additional information on this award, including the abstract, can be found on CDMRP’s website at

http://cdmrp.army.mil/search.aspx , by selecting ”2008” under Fiscal Year and entering the last name of  the Principal Investigator under PI Last Name.

Weight Gain in Kids on Antipsychotic Medicines

It has been known for several years that antipsychotic medications can cause weight gain in adults and increase the risk for serious metabolic disorders. Scientists at The Zucker Hillside Hospital and The Feinstein Institute for Medical Research embarked on a large study following children and adolescents who have been prescribed antipsychotic medicines for the first time and examining the impact they had on weight gain and metabolic changes. Indeed, researchers identified a worrisome degree of weight gain and caution their colleagues to take these changes seriously. Weight gain and changes in blood glucose and lipid metabolism can be precursors of diabetes, hypertension, metabolic syndrome, stroke and heart attack. The children tested were between 4-19 years old.

    "The data sheds further light on the frequency and severity of weight gain associated with these newer antipsychotics,” said Christoph U. Correll, MD, medical director of the Recognition and Prevention (RAP) program at the Zucker Hillside Hospital and a scientist in the Feinstein Institute’s Center for Psychiatric Neuroscience. “Our findings suggest increased caution in prescribing them to pediatric patients.”

    The scientists studied 272 young people who had been prescribed antipsychotic medicines for a range of serious behavioral, mood and psychosis-related problems. The patients were prescribed one of a number of second-generation antipsychotics and followed over the first 12 weeks to assess changes in weight, blood glucose and lipids. At around 11 weeks, the young patients had gained an average of 19 pounds on the antipsychotic, olanzapine; 13.5 pounds on quetiapine; 11.9 pounds on risperidone; and 9.9 pounds on aripiprazole. By comparison, 15 patients who refused participation in the study or were not compliant with taking the antipsychotics were used as a control group and their weight gain during the same study period was less than a half-pound.

    The findings were published this week in the Journal of the American Medical Association (JAMA).

    The scientists also identified substantial changes in triglycerides and cholesterol, and found that the weight gain alone did not seem to explain entirely the adverse metabolic effects that varied significantly across the individual medications. All of the findings, Dr. Correll said, “should be considered when choosing antipsychotics.” SATIETY (Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth) is the largest cohort study of atypical antipsychotic treatment in children and adolescents treated with antipsychotics. It is also the largest study of its kind in children or adults who received antipsychotic treatment for the first time in their life. This is a key study feature because prior treatment can obscure the true cardiometabolic effects of medications. In the SATIETY study, the antipsychotic-naïve youths suffered from a range of problems, including psychosis (30.1 percent,) mood disorders (47.8 percent) and aggressive behavior (22.1 percent).  Researchers followed these patients to understand if weight and metabolic changes are due to the new onset of a psychiatric illness or related hospital admission, or whether the observed changes are effects of the antipsychotic treatment.

    The scientists found that the worsening of metabolic parameters differed between the antipsychotic medications groups, despite the shared, large and significant changes in body weight parameters, including waist circumference. Olanzapine, which was also associated with the largest effects on body weight, was associated with the greatest and most widespread worsening of lipid as well as glucose parameters. Quetiapine and risperidone were associated with varying degrees of lipid abnormalities only, which were more pronounced with quetiapine. By contrast, aripiprazole was not associated with any significant worsening in glucose or lipid parameters, which was also the case in the comparison subjects.  “These findings provide further evidence for an additional, weight independent mechanism for glucose and lipid abnormalities with olanzapine that does not seem to be shared by the other antipsychotics that were studied,” said Dr. Correll.

    Antipsychotic medication use in young people has grown substantially in recent years and this study calls into question the effects of this upward trend.  “Abnormal childhood weight and metabolic status adversely affect adult cardiovascular outcomes via continuation of these risk factors or independent or accelerated mechanisms,” the scientists wrote. “Our results, together with data from first-episode studies, suggest that guidelines for antipsychotic medication exposure for vulnerable pediatric and adolescent patients naive to antipsychotic medication should consider more frequent (e.g., biannual) cardiometabolic monitoring after the first three months of treatment. Finally, in view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medications must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management.”

    In an accompanying editorial, Christopher K. Varley, M.D., and Jon McClellan, M.D., of Seattle Children’s Hospital, said that while “these medications can be lifesaving for youth with serious psychiatric illnesses such as schizophrenia, classically defined bipolar disorder, or severe aggression associated with autism,” and “given the risk for weight gain and long-term risk for cardiovascular and metabolic problems, the widespread and increasing use of atypical antipsychotic medications in children and adolescents should be reconsidered.”

    This study was, in part, supported by the Feinstein's General Clinical Research Center.

About The Feinstein Institute for Medical Research

Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in cancer, leukemia, lymphoma, Parkinson's disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, neuroimmunology, and medicinal chemistry.  Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient, annually enrolling some 10,000 subjects into clinical research programs. 

About The Zucker Hillside Hospital

The Zucker Hillside Hospital is home to many of the nation’s experts on severe mental illness. In addition to treating patients in and out of the hospital, psychiatric research has been ongoing for decades and includes landmark studies on the treatment and course of first-episode psychotic patients. Genetics also plays a critical role in severe mental illness and scientists at the Zucker Hillside Hospital have identified several important risk genes. John Kane, MD, chair of psychiatry at Zucker Hillside, and his team of scientists recently received a $26 million federal grant to train psychiatric staff across the country to deliver state-of-the-art treatments for patients with a first episode of schizophrenia and to test whether it works to delay or alter the disabling course of the illness.

Lymphatic Research Foundation Launches Tissue Bank at the Feinstein

The Lymphatic Research Foundation has launched the National Lymphatic Disease and Lymphedema Patient Registry and Tissue Bank in collaboration with Dr. Peter K. Gregersen and his colleagues at The Feinstein Institute for Medical Research. This registry will enable scientists and clinicians to better understand the course of lymphedema and other lymphatic diseases. Collecting medical data and identifying genetic fingerprints of the condition is critical in understanding the nature and the progression of these conditions. The Patient Registry has already begun and the Tissue Bank (Biorepository) will begin early next year. Robert Lundsten and the Feinstein Institute's Biomedical Informatics Group created and rolled out the LRF registry. For more information contact the Lymphatic Research Foundation at 516-625-9675.

Feinstein scientist Todd Lencz, PhD, gets federal GO award to study schizophrenia

The National Institutes of Health (NIH) has awarded a “Grand Opportunity” (GO) grant to a team of researchers – led by Todd Lencz, PhD, at The Feinstein Institute for Medical Research and Zucker Hillside Hospital, and Ariel Darvasi, PhD, of Hebrew University – to use cutting-edge technologies to help unravel the genetic basis of schizophrenia. More than two million dollars was awarded to the team, which also includes Anil Malhotra, MD, and Peter Gregersen, MD, of the Feinstein Institute and David Goldman, MD, of the National Institute of Alcohol Abuse and Alcoholism, to conduct this research.

    As described by the NIH, the GO grant program was designed to support “high impact ideas” that can “accelerate critical breakthroughs” in our understanding of human disease. The program was made possible by an infusion of money to the NIH under the American Recovery and Reinvestment Act (also known as the “economic stimulus package”), representing “the single largest boost to biomedical research in history,” according to President Barack Obama. In announcing the awards, President Obama singled out genetic research as “one of the most exciting areas of research to move forward as a result of this investment.” Eventually, it is hoped that this research may be used to more accurately predict, treat, and prevent serious mental illnesses such as schizophrenia.

    It has long been known that schizophrenia – a complex brain disease marked by hallucinations and delusions – tends to run in families and therefore has a genetic component to its cause. However, scientists have struggled to conclusively identify the genes that contribute to risk for this disease. “Current evidence suggests that many genes are likely to be involved in schizophrenia, which theoretically should provide a large target for scientists,” Dr. Lencz said. “Unfortunately, these genes are individually either very rare or very weak in effect, making them very elusive to traditional forms of genetic analysis.”

    The newly funded GO grant builds on prior gene-hunting efforts with several distinctive features. Most notably, the sample consists entirely of individuals (patients and controls) of Ashkenazi Jewish descent, recruited in Israel by Dr. Darvasi, who explains “The unique demographic history of the Jewish Ashkenazi population results in a more homogeneous genetic background compared to the general population. This should allow disease-related genetic signals to stand out more clearly in our analyses.” Additionally, this study will utilize the most advanced genetic technologies, which will permit examination of many more pieces of the genetic code than prior generations of research.

Newsday series on Alzheimer's includes interview with Feinstein scientists

http://www.newsday.com/news/health/tracking-what-triggers-onset-of-alzheimer-s-disease-1.1510232