About INBRAIN
October 2006Name of proposed IU Center of Excellence: Indiana Center for Biomarker Research in Neuropsychiatry (INBRAIN)
Goal:
State of the art regional tissue and brain bank for biomarker discovery through genomics, proteomics and integrative studies of major neuropsychiatric disorders- schizophrenia, bipolar disorder, depression, autism, alcoholism and other substance abuse, linked to current work done at IPR, SNRI and Riley, as well as Lilly donor sample capabilities. Why biomarkers? There are to date no clinical laboratory blood tests for psychiatric disorders. Given the complex nature of psychiatric disorders, the current reliance on patient self-report of symptoms and the clinician’s impression on interview of patient is a rate limiting step in delivering the best possible care with existing treatment modalities, as well as developing new and improved treatment approaches, including new medications. We have developed an approach for identifying molecules in the blood that reflect illness in the brain. These molecules can be used to develop clinical laboratory tests to aid: 1) diagnosis of illness, 2) early intervention and prevention efforts, as well as 3) prognosis of course of illness and 4) monitoring response to various treatments, including medications. In conjunction with other clinical information, such tests will play an important part of personalizing treatment to increase effectiveness and avoid adverse reactions- personalized medicine in psychiatry. Moreover, they will be of immediate use to pharmaceutical companies engaged in new neuropsychiatric drug development efforts, at both a pre-clinical and clinical (Phase I, II and III) stages of the process.
Background material and proposed research academic focus:
Human postmortem brain tissue banks for scientific study suffer from one or more of three major caveats: 1) incomplete pre-mortem history on the donor brain; 2) scarcity of material, and 3) technical quality of the material, including lack of toxicology (medications, drugs) on the collected samples. In addition to classical neuropathology, with the advent of microarray technology, proteomics, and bioinformatics, the opportunity to do groundbreaking work with human brain tissue has never been better. A group of faculty involved in psychiatric and neuroscience research at IU School of Medicine, together with researchers from Eli Lilly, began meeting in 2005 to explore the possibility of building a local state-of-the-art tissue and brain bank, as a way of opening new avenues for individual researchers, and fostering academic –industry partnerships.Existing strengths in proposed area:
The consensus of our study group was: 1) a local tissue and brain bank for psychiatric disorders would be a useful resource; 2) we can learn from existing brain banks across the country in terms of implementing their strong features and minimizing their weakness to build a top tier and accessible regional brain bank, and 3) we can build on Lilly’s tissue cataloging software tool (CATD) and regional tissue\fluid collection capabilities which would allow collection of multiple samples from single donors to encourage “systems biology” level studies. To our knowledge no other brain bank is attempting to collect blood, CSF, vitreous fluid, urine, and brains from single donors -which would make this a unique resource for systems-level investigations.Justification for uniqueness and interdisciplinary nature of the center:
INBRAIN is, uniquely and programmatically, designed to have three arms: a pre-clinical animal model arm, a live human subject arm, and a postmortem tissue arm (Figure 1). The pre-clinical animal model arm will build on existing animal model work at IPR, SNRI and Eli Lilly involving molecular changes in models of neuropsychiatric disorders. The live subject arm will focus on collecting blood samples from neuropsychiatric patients which are well characterized clinically, for biomarker research. The postmortem arm will collect brains, tissues and fluids from donor subjects with neuropsychiatric disorders, focusing on an integrative system biology approach. The Venn diagram overlap of synergistic results obtained through pre-clinical model work, live human subject blood profiling, and postmortem work will greatly aid in the identification of peripheral biomarkers of neuropsychiatric disorders. Such biomarkers would be of exceptional utility in terms of developing laboratory diagnostic and prognostic tests for clinical practice, as well as for aiding clinical trials of new candidate pharmacotherapeutic agents.Anticipated sources and amount of funding:
This is anticipated to be a long-term project, with significant local, national and international impact. Initial INBRAIN location is in generous space provided by the Institute for Psychiatric Research, IUPUI. Eli Lilly has generously provided start-up funding since the beginning of 2006 for sample collection, personnel percentage time, microarrays, and equipment (freezer, ABI 7300 quantitative PCR machine). IRB protocols have been approved, preclinical model data has been collected, as well as blood samples from prospective live donor cohorts and the first two postmortem brains with peripheral tissue/ fluids samples. NIH Grant support will be actively pursued starting with year 2 of the project, as the first data using this resource is generated. It is expected that at least half of the operating costs of the facility will come from grant sources and the balance from industry and other private sources (foundations, philanthropy). In the long-term, the intellectual property, patents and start-up companies generated by research under the aegis of INBRAIN may be another source of independent financial support.Planned scholarly activities (conferences, workshops, exhibits, journals, etc.):
INBRAIN, through the Department of Psychiatry, IPR and SNRI, has already hosted at IU School of Medicine over the last year seminars by three of the leading national experts on neuropsychiatric brain and tissue banking: Dr. Francine Benes from Harvard, Dr. Mark Vawter from University of California, Irvine/Pritzker Consortium Brain Bank, and Dr. Manuel Casanova from University of Louisville, an expert on autism. These three experts have agreed to serve as external advisers to INBRAIN. Dr. Niculescu and Dr. Nurnberger have visited Dr. Francine Benes and the Harvard Brain Bank on a fact-finding visit in October 2005. Dr. Niculescu has also visited Dr. Mark Vawter and the UC Irvine Brain Bank in March 2006. We plan to have a regular quarterly meeting of our internal SAB (Scientific Advisory Board), comprised of the investigators listed above, as well as yearly meetings of the external SAB, comprised of Drs. Benes, Vawter, Casanova, and one other intended expert: Dr. Joel Kleinman from National Institute of Mental Health. It is our intent to have the yearly external SAB meetings be part of a full-day conference, open to local and national participants, focused on neuropsychiatric biomarker research. A summary of the yearly conference will be published in the international journal Psychiatric Genetics, of which Dr. Nurnberger is Editor in Chief, and Dr. Niculescu is Assistant Editor. The scientific results of work done by INBRAIN will be communicated in national and international conferences, as well as submitted for publication in top quality peer-reviewed journals.