A Novel Approach to Stroke Treatment: Acid-Sensing Iion Channel Inhibitors

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$118,342.00
Award Year:
2009
Program:
STTR
Phase:
Phase I
Contract:
1R41NS064845-01
Award Id:
94059
Agency Tracking Number:
NS064845
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
VIROGENOMICS, INC., 9020 SW WASHINGTON SQUARE RD, TIGARD, OR, 97223
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
045283590
Principal Investigator:
ROGER SIMON
(503) 413-5454
RSIMON@DOWNEUROBIOLOGY.ORG
Business Contact:
GILBERT MILLER
() -
gil.miller@virogenomics.com
Research Institution:
EMANUEL HOSPITAL AND HEALTH CENTER

EMANUEL HOSPITAL AND HEALTH CENTER
1225 NE 2ND AVENUE
PORTLAND, OR, 97232-6869

Domestic nonprofit research organization
Abstract
DESCRIPTION (provided by applicant): Stroke is the third leading cause of death and a leading cause of serious, long-term disability in the United States. Although in recent years enormous progress has been made towards defining the cellular and molecular responses of the brain to ischemia, our knowledge is not yet adequate to protect against ischemic injury. No neuroprotective agents of demonstrable efficacy have yet passed clinical trials. However, we do know that calcium entry is the central feature of i schemic brain injury. Blockade of calcium entry prevents brain cell death during stroke. In a search for other effectors of brain injury in the setting of ischemia, our attention has been drawn to the recently discovered family of acid-sensing ion channels (ASICs). As acidosis is a central and prominent metabolic feature of ischemic brain and as ASICs are capable of Ca2+ permeability we have hypothesized a pathological function of ASIC's in ischemic brain injury. Members of this ion channel family respond t o acidic stimuli and would therefore be activated by that central feature of ischemia, acidosis and in that setting, would flux Ca2+. Our colleagues and we have offered recent data, to include Ca2+ imaging, showing that ASIC channels flux Ca2+ in native ne urons in a pH dependent manner. We have shown that this Ca2+ flux is markedly potentiated by modeled ischemia and that this Ca2+ flux is glutamate independent. ASICs are expressed throughout the mammalian central nervous system where they function in synap tic plasticity, learning and memory. Their ubiquitous presence makes them potentially important modulators of brain injury in the setting of ischemia. The discovery of ASIC blockade is the first discovery in 20 years of a new, potent mechanism to prevent c alcium toxicity in acute stroke. The aim of this proposal is to advance the development of inhibitors of ASIC channels towards the creation of an acute stroke therapeutic. PUBLIC HEALTH RELEVANCE: Stroke is the third leading cause of death and a leading ca use of serious, long-term disability in the United States. Blockade of calcium entry prevents brain cell death during stroke. The discovery of ASIC blockade is the first discovery in 20 years of a new, potent mechanism to prevent calcium toxicity in acute stroke.

* information listed above is at the time of submission.

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