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Novel Therapeutic Opportunity in Stroke

Award Number: R41NS087684
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2014
PERIOD OF PERFORMANCE END DATE: 03/31/2015

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Novel Therapeutic Opportunity in Stroke - DESCRIPTION (provided by applicant): Stroke is a leading cause of death and disability in the USA, yet widely effective treatments remain elusive and, except for a lengthy program of rehabilitation, no effective treatment for cerebral ischemic stroke is available. Therefore, there s a critical need in new therapeutic approaches which can maximally preserve ischemic penumbra and facilitate functional recovery. In the last two decades substantial efforts have been invested in developing anti-stroke medicine, but these efforts have not resulted in clinically-efficacious therapies for stroke. These failures highlight the need for development of new therapeutic ideas and approaches for prevention of neuronal injury secondary to ischemia and stroke. Among possible strategies, effective post-stroke treatments with broad therapeutic windows are likely to be the most valuable because of the unexpected nature of stroke. The existing literature and preliminary data presented indicate that activation of 7 nicotinic acetylcholine receptors (nAChRs) can significantly reduce brain injury and neurological deficits caused by ischemic injury. A novel therapeutic paradigm has been introduced that converts endogenous choline/ACh into potent therapeutic agents in cerebral ischemia by inhibiting 7 nAChR desensitization using Type-II positive allosteric modulators (i.e. PAMs-II), such as PNU-120596. Our preliminary data demonstrate that PNU-120596 administered intravenously up to 6 hours after the onset of focal cerebral ischemia significantly reduces infarct volume and improves neurological function in a middle cerebral artery occlusion (MCAO) model of cerebral ischemic stroke in rats and suggest that novel PAM-II agents represent a novel therapeutic opportunity in cerebral stroke. The path for discovery and proof-of-concept phases includes: A) synthesis of novel candidate molecules with appropriate calcium flux activity, stability, selectivity, solubility and drug-like characteristics for eventual use in in vivo efficacy studies;and B) a detailed functional activity assessment of PAM-II candidate profiles in acute rat brain slices We expect to identify novel leads with suitable drug-like properties for testing this novel concept in the context of a new therapy for cerebral ischemic stroke.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2014 ( Subtotal = $225,000 )
2014	2014	EPIGEN BIOSCIENCES INC	10225 BARNES CANYON ROAD	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/1/2014	NEW	$225,000
														Subtotal = $225,000

Grand Total All Awards = $225,000

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Novel Therapeutic Opportunity in Stroke

Award Number: R41NS087684

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2014

PERIOD OF PERFORMANCE END DATE: 03/31/2015

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