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Identification of Oligodendrocyte Stimulators

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
89391
Program Year/Program:
2010 / SBIR
Agency Tracking Number:
NS060188
Solicitation Year:
N/A
Solicitation Topic Code:
NINDS
Solicitation Number:
N/A
Small Business Information
JS GENETICS, LLC
RICHARD CHAMPAGNE 397 POST ROAD, SUITE 203 DARIEN, CT -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2010
Title: Identification of Oligodendrocyte Stimulators
Agency: HHS
Contract: 2R44NS060188-02A1
Award Amount: $708,235.00
 

Abstract:

DESCRIPTION (provided by applicant): Oligodendrocytes (OLs) are the myelinating cells of the central nervous system and play a critical role in white matter formation. Serious clinical disorders affect central nervous system white matter during early devel opment. These conditions include periventricular white matter injury (PWMI), which affects up to 20% of very low birth weight premature infants. PWMI is due to loss of Pre- oligodendrocytes (PreOLs), which are proliferative cells that develop into myelinat ing OLs. Presently, we are unaware of pharmacological approaches that specifically target PreOLs, resulting in increased proliferation of these cells. Because white matter injury is the leading cause of nervous system injury in premature infants, developi ng new treatments for PWMI will have a major clinical impact. Under Phase 1 of this SBIR, we proposed to use high-throughput screening to identify compounds ( hits ) that would stimulate PreOL proliferation. These studies proved to be highly successful, a s we identified diazoxide as a stimulator of PreOL proliferation, and we observed that this compound promotes myelination in a murine model of PWMI. Diazoxide acts by activating KATP channels, and we were able to demonstrate KATP channel component expressi on in PreOLs. We also found that other KATP activators stimulate PreOL proliferation. Thus, we achieved the major goal of our Phase 1 proposal. In Phase II studies, we propose to extend our study of diazoxide in preclinical, proof-of-concept studies invol ving cell culture and animal studies. We will: (1) Define OL-stage specific responses to diazoxide. (2) Evaluate protection against PWMI in animal models. (3) Assess long-term effects of neonatal diazoxide therapy. The long-term goal of this work is to de velop novel therapeutic agents for the treatment of white matter injuries in premature infants. Support from the NIH through the SBIR program will serve to strengthen the productive academic/industrial collaboration established between scientists at Yale U niversity (Dr. Rivkees) and JS Genetics (New Haven, CT) to discover novel drugs. Ultimately, research such as this will lead to important discoveries with significant public health benefit and commercial value. We also anticipate that these studies will le ad to the development of novel approaches for treating and preventing white matter injury in the tens of thousands of premature infants born and hospitalized each year. PUBLIC HEALTH RELEVANCE: The goal of this work is to assess the utility of diazo xide as a therapeutic agent for the treatment of white matter injuries in premature infants. We anticipate that these studies will lead to the development of novel approaches for treating and preventing white matter injury in the tens of thousands of prema ture infants born and hospitalized each year.

Principal Investigator:

Seiyu Hosono
2035708275
S.HOSONO@JSGENETICS.COM

Business Contact:

Seiyu Hosono
a.mireskandari@jsgenetics.com
Small Business Information at Submission:

JS GENETICS, INC.
Alidad Mireskandari 15 Ketchum Street Westport,, CT -

EIN/Tax ID: 180052482
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No