SBIR-STTR Award

Discovery of Novel Drugs for Autism
Award last edited on: 3/25/2019

Sponsored Program
STTR
Awarding Agency
NIH : NIMH
Total Award Amount
$771,464
Award Phase
2
Solicitation Topic Code
101
Principal Investigator
Zhen Yan

Company Information

ASDDR LLC

9 Vassar Drive
Getzville, NY 14068
   N/A
   N/A
   www.asddr-us.com

Research Institution

Calspan UB Research Center

Phase I

Contract Number: 1R41MH112237-01A1
Start Date: 6/29/2017    Completed: 5/31/2019
Phase I year
2017
Phase I Amount
$388,482
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

Phase II

Contract Number: 5R41MH112237-02
Start Date: 6/29/2017    Completed: 5/31/2019
Phase II year
2018
Phase II Amount
$382,982
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 1. 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 Shank3-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, Shank3-deficient mice and BTBR mice. Aim 2. 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 Shank3-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.

Thesaurus Terms:
Actins; Address; Adverse Effects; Animal Model; Anti-Cancer; Antineoplastic Agents; Autistic Disorder; Base; Behavior; Behavioral; Benchmarking; Biochemical; Brief Intervention; Btbr Mouse; Buffaloes; C-Terminal; Chromatin Remodeling; Chromatin Remodeling Factor; Clinical; Commercialization; Development; Dna Sequence Alteration; Dose; Drug Development; Drug Discovery; Drug Screening; Drug Targeting; Electrophysiology (Science); Enzymes; Epigenetic Process; Epigenetic Regulation; Etiology; Event; Exome Sequencing; Exons; Fda Approved; Foundations; Functional Disorder; Future; Genes; Genetic; Genetic Transcription; Genome; Genome-Wide; Glutamate Receptor; Glutamates; Goals; Histone Acetylation; Histone Deacetylase; Histone Deacetylase Inhibitor; Histones; Immunoblotting; Impairment; Intervention; Investigational New Drug Application; Laboratories; Lead; Link; Maintenance; Malignant Neoplasms; Mediating; Mental Disorders; Modeling; Molecular; Molecular Target; Mouse Model; Mus; Neurodevelopmental Disorder; Neurons; New York; Novel; Novel Therapeutics; Outcome; Patch Clamp; Pathogenicity; Pathway Interactions; Pharmaceutical Preparations; Pharmacology; Phase; Phase 1 Study; Phase 2 Study; Preclinical Study; Prefrontal Cortex; Protein Expression; Protein Family; Protein Function; Repetitive Behavior; Research; Risk Factors; Risk Variant; Safety; Scaffolding Protein; Social; Social Interaction; Solid; Symptoms; Synapses; Synaptic Function; Testing; Therapeutic; Tool; Toxic Effect; Transcriptional Regulation; Transcriptome Sequencing; Treatment Efficacy; Universities;