Discovery of Novel Drugs for Autism

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41MH112237-01A1
Agency Tracking Number: R41MH112237
Amount: $388,482.00
Phase: Phase I
Program: STTR
Awards Year: 2017
Solicitation Year: 2014
Solicitation Topic Code: 101
Solicitation Number: PA14-196
Small Business Information
9 VASSAR DR, Getzville, NY, 14068-1289
DUNS: 079914378
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: N
Principal Investigator
 ZHEN YAN
 (716) 829-3058
 zhenyan@buffalo.edu
Business Contact
 MARTINA TSAI
Phone: (716) 316-8457
Email: asddr.aor@gmail.com
Research Institution
 CALSPAN-UNIVERSITY OF BUFFALO RES CENTER
 BOX 400, 4455 GENESEE ST
BUFFALO, NY, 14225-1955
 Domestic nonprofit research organization
Abstract
Summary The goal of this study is to discover novel mechanism based pharmacological intervention for autism a devastating neurodevelopmental disorder with no treatment currently Genetic sequencing has revealed extensive overlap in risk genes for autism and for cancer many of which are chromatin remodeling factors important for transcriptional regulation suggesting the possibility of repurposing the anti cancer drugs targeting epigenetic enzymes for autism treatment ASDDR LLC and Yan Lab at SUNY Buffalo propose to jointly investigate the hypothesis that histone deacetylase HDAC inhibitors are able to restore the expression of key autism risk factors and induce long lasting rescue of autism like behavioral and synaptic deficits Combined behavioral biochemical and electrophysiological approaches will be used to address two specific aims Aim To discover HDAC inhibitors that can alleviate autism like behavioral deficits in autism mouse models Yan lab screened a number of drugs and found that a brief treatment with the highly potent and class I specific HDAC inhibitor romidepsin Istodax an FDA approved anti cancer agent at the very low dose led to dramatic and prolonged rescue of the social deficits in the Shank deficient mouse model of autism To determine whether this pharmacological agent can serve as a tool compound for autism drug development its therapeutic efficacy and safety will be examined in two different models of autism Shank deficient mice and BTBR mice Aim To identify the molecular targets of HDAC inhibitors as benchmarks for the treatment of autism For the discovery of effective drugs to treat autism the molecular pathways on which HDAC inhibitors act to alleviate the autism like behavioral deficits in Shank deficient mice need to be understood We will reveal the potential benchmark such as actin regulators and NMDARs as molecular targets of romidepsin This phase I preclinical study will provide great promise for the discovery of new and effective pharmacological agents to treat the social interaction deficits a core symptom of autism Project Narrative This project is to discover novel mechanism based therapeutic strategies for autism The corporate and academic partners propose to jointly investigate the hypothesis that histone deacetylase HDAC inhibitors are able to restore the expression of key autism risk factors and induce long lasting rescue of autism like behavioral and synaptic deficits

* Information listed above is at the time of submission. *

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