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Novel NMDA-targeted Therapy for Alzheimer's Disease

Award Number: R43AG047709
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2014
PERIOD OF PERFORMANCE END DATE: 07/31/2016

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Novel NMDA-targeted Therapy for Alzheimer's Disease - Abstract Memantine, an aminoadamantane, is approved to treat moderate-to-severe Alzheimer's disease in the US and in Europe. Memantine selectively inhibits abnormally active N-methyl-D-aspartate-type glutamate receptor (NMDAR) channels, while preserving normal glutamate activity and physiological neuronal function (Lipton, 2006; Lipton, 2007a,b). Pathological NMDA receptor activity is further down-regulated by Snitrosylation of cysteine residues located on the N-terminus or extracellular domain. Taking advantage of these insights, PRI has developed a proprietary series of bifunctional antagonists, called nitromemantines, that not only preferentially bind to the open-channel state but also selectively target NO to a second modulatory site using the memantine pharmacophore as a homing motif (Wang, 2006, Wang et al. patents). Our data suggest that some of these memantine analogs have good potency, while maintaining selectivity for persistently open NMDAR channels. Most importantly, they appear to have greater neuroprotective properties than memantine in both in vitro and in vivo animal models. Recent work from the laboratory of our collaborator and co-inventor, Professor Stuart Lipton (Burnham Institute) demonstrates the unique ability of one of our nitromemantines (YQW-036, 1-amino-3,5-diethyl-7-nitrateadamantane) to rescue/protect synapses perhaps by superior inhibition of pathogenic extrasynaptic NMDARs (Talantova, 2013) This animal POC combined with the demonstrated safety of nitromemantines support the translation of this basic science work into clinical stage evaluation. Hence, our overall goal is to initiate preclinical studies to support submission of an IND for YQW-036. This effort will begin with Phase I pharmacokinetics and safety studies of YQW-036 as a potential development candidate. Successful completion of the Phase I studies will merit submission of a Phase II application to support IND enabling studies that are required prior to human clinical trials. Successful achievement of these milestones will provide a proprietary first-in-class disease-modifying drug for Alzheimer's disease.


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: 2020 ( Subtotal = -$649 )
2020	2014	PANORAMA RESEARCH	1230 BORDEAUX DR	SUNNYVALE	CA	94089	SANTA CLARA	USA	Aging Research	000	1	10/1/2019	NEW	-$649
														Subtotal = -$649

Issue Date FY: 2017 ( Subtotal = -$4,218 )
2017	2014	PANORAMA RESEARCH	1230 BORDEAUX DR	SUNNYVALE	CA	94089	SANTA CLARA	USA	Aging Research	000	1	1/31/2017	NEW	-$4,218
														Subtotal = -$4,218

Issue Date FY: 2014 ( Subtotal = $224,667 )
2014	2014	PANORAMA RESEARCH, INC	2462 WYANDOTTE STREET	MOUNTAIN VIEW	CA	94043	SANTA CLARA	USA	Aging Research	000	1	8/11/2014	NEW	$224,667
														Subtotal = $224,667

Grand Total All Awards = $219,800

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Novel NMDA-targeted Therapy for Alzheimer's Disease

Award Number: R43AG047709

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2014

PERIOD OF PERFORMANCE END DATE: 07/31/2016

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