NIH Grant to support Mount Sinai Research Program to Create Biological Network Model of Alzheimer’s Disease in …

New York (PRWEB) September 18, 2013

Scientists from the Icahn School of Medicine at Mount Sinai, in partnership with the New York Stem Cell Foundation (NYSCF), and other institutions, have been awarded a multi-year grant from the National Institutes of Health (NIH) to study Alzheimers disease.

This study will apply innovative analytical methods to large-scale molecular, cellular, and clinical data from Alzheimers patients to construct biological network models and gain new insights into the complex mechanisms of the disease, and identify potential therapeutic targets. Biological network models are complex mathematical representation of large amounts of data. These networks provide a unified map that integrates not only the key genes involved in a disease but also the biological pathways that those genes control.

The NIH grant will enable the research team at Mount Sinai and partner institutions to build upon the discovery published earlier this year in the journal Cell of a network of genes as a key mechanism driving Late Onset Alzheimers Disease (LOAD) through involvement in the inflammatory response in the brain.

Eric Schadt, PhD, The Jean C. and James W. Crystal Professor of Genomics at the Icahn School of Medicine at Mount Sinai, and Director of the Icahn Institute for Genomics and Multiscale Biology, will be a principal investigator in the study. With this grant, we can continue to build and refine our predictive model of Alzheimers disease to yield valuable insights into the complex mechanism of the disease and potential therapies. In the same way that sophisticated predictive mathematical models drive decision making in the global financial markets, our field of medical research has begun to rely on network models to derive meaning from vast amounts of patient data, enabling better understanding and treatment of human disease, said Dr. Schadt.

The research team will use several cellular and animal models to validate the actions of individual genes, as well as entire molecular networks predicted to drive the disease. The team will also employ a computational approach to test if any existing drugs currently used for other conditions are capable of modulating the Alzheimers networks and can, therefore, be repurposed for Alzheimers disease treatment or prevention.

This award was among several new research grants totaling $45 million NIH announced on Wednesday to advance the National Plan to Address Alzheimers Disease, a national effort that aims to find effective interventions for Alzheimers by 2025. Dr. Neil Buckholtz, Director of the Division of Neuroscience at the National Institute on Aging, which leads the NIH Alzheimers research program, noted that the array of grants will fund innovative basic research as well as new clinical trials aimed at finding therapies to prevent the disorder. We are delighted to support Dr. Schadt and his team in their important work of applying novel analytical methods to build models of this complex disorder, Buckholtz said. Additionally, this funding supports their computational approach investigating the repurposing of existing drugs as treatment for Alzheimers-- a key objective set forth in the Alzheimers Plan.

Scott Noggle, PhD, Director of the NYSCF Laboratory and the NYSCF Charles Evans Senior Research Fellow for Alzheimers Disease, is a principal investigator in the study. Dr. Noggle and his team at NYSCF will be the lead stem cell partner in this study. They will generate stem cell lines from Alzheimers patient samples and produce Alzheimers neurons that will be used as a platform for validating drug targets that are identified through computational analysis. Stem cell lines and neurons will be produced on the unique NYSCF Global Stem Cell ArrayTM, a proprietary automated technology platform that for the first time makes it possible to create identical stem cell lines from a large number of patients in a massively parallel process. Existing approaches have failed to identify new Alzheimers therapeutics and I believe that through this multifaceted approach we will collaborate to identify and validate new drug targets for Alzheimers patients, said Dr. Noggle.

Sam Gandy, MD, PhD, Director of the Center for Cognitive Health at Mount Sinai, and a principal investigator in the study, said, This research is of paramount importance. Currently, no effective disease-modifying or preventive drugs exist for common, late onset Alzheimers Disease. Despite decades of intensive conventional research, the causal chain of mechanisms behind sporadic Alzheimers Disease has remained elusive. This multi-scale, computational strategy, combined with target validation in mouse brain, in fly brain, and in stem cell models, is already providing clues to unanticipated pathways and new drug discovery opportunities.

The NIH grant (NIA grant AG 046170-01) was developed under a recent initiative specifically aimed at understanding the complexity of Alzheimers disease. This approach assumes that Alzheimers might best be explained and treated by focusing on genes that serve as hubs that interconnect a group of genes. These hubs are important because when they malfunction and cause Alzheimers, they cause predictable malfunctions of the entire group of connected genes. This approach leverages big data and high-end analytical approaches to develop predictive network models of disease. As a key source of data, the Mount Sinai investigators will study gene expression in brains from the Mount Sinai Alzheimers Disease Research Center Brain Bank that specializes in identifying the very earliest stages of Alzheimers. This brain bank was established over 35 years ago and is considered to be one of the best such resources in the world.

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NIH Grant to support Mount Sinai Research Program to Create Biological Network Model of Alzheimer’s Disease in ...