Novel Neuroprotectants for TBI

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41NS061459-01
Agency Tracking Number: NS061459
Amount: $128,100.00
Phase: Phase I
Program: STTR
Awards Year: 2008
Solicitation Year: 2008
Solicitation Topic Code: N/A
Solicitation Number: PHS2007-2
Small Business Information
DUNS: 791384774
HUBZone Owned: Y
Woman Owned: Y
Socially and Economically Disadvantaged: Y
Principal Investigator
 () -
Business Contact
Phone: (404) 727-4190
Research Institution
DESCRIPTION (provided by applicant): There are no FDA approved pharmacological therapies for the acute treatment of traumatic brain injury (TBI) that mitigate damaging neurological effects. However, the potential for effective pharmacological intervention exists in that a majority of post-traumatic degeneration results from pathochemical and pathophysiological cascades of secondary events that occur in the minutes, hours and even days after the primary mechanical damage to tissue. Early factors in these sec ondary cascades include excessive release of the excitatory neurotransmitter glutamate, NMDAR over stimulation, a massive increase in intracellular calcium, mitochondrial metabolic failure and activation of the proteolytic enzyme calpain. Despite ample dem onstration that targeting glutamate receptor-mediated excitotoxicity is neuroprotective in various animal models of neurological injury; no NMDAR antagonist has shown adequate efficacy and safety to be approved in man for TBI. Reasons frequently cited for the clinical failure of NMDAR antagonists include unacceptable side effects that required dosing regimes lower than needed for maximum efficacy and the administration of drug too long after the insult. Early generations of NMDAR antagonists (channel blocke rs, and competitive blockers of glutamate or glycine binding) were associated with significant psychotic and cardiovascular side effects. NMDAR antagonists that selectively interact with NMDA receptors containing the NR2B subunit as noncompetitive alloster ic antagonists are better tolerated than prior generation NMDAR blockers. One in this class, CP101606, yielded promising results in a phase IIa study in TBI patients. Recently, NeurOp, Inc showed that a new generation of NR2B specific NMDAR blockers under development having a unique disease activated mechanism offer potent neuroprotection in animal models of ischemia. Exemplary of the class, NeurOp's 93-31 exerts minimal NMDAR antagonism at normal pH but offers potent NMDAR block at the reduced pH known to accompany ischemia. By blocking NMDAR only when and where needed, pH sensitive NMDAR antagonists are expected to offer a much improved therapeutic index over prior generation drugs. In this project we shall explore whether the pH drop that accompanies TBI is adequate to activate NeurOp's 93-31, and whether this compound provides neuroprotection in an animal model of TBI. Narrative: About 1.5 million people suffer traumatic brain injury in the US each year. Thousands experience long lasting brain injury that interferes with their ability to lead productive and full lives. We plan to test a promising new class of therapeutics for traumatic brain injury.

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

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government