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TARGETED PARAOXONASE FUSION PROTEIN AS A NEUROTHERAPEUTIC FOR NERVE GAS AGENTS

Award Number: U44NS057843
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2006
PERIOD OF PERFORMANCE END DATE: 05/31/2010

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TARGETED PARAOXONASE FUSION PROTEIN AS A NEUROTHERAPEUTIC FOR NERVE GAS AGENTS - DESCRIPTION (provided by applicant): Civilian populations are at risk for exposure to chemical nerve gas agents such as organophosphates (OPs). These compounds affect both the peripheral nervous system (PNS) and the central nervous system (CNS). The CNS is affected because the OPs are lipid-soluble small molecules that easily penetrate the brain, owing to transport across the blood-brain barrier (BBB). Owing to the effects in the CNS, those individuals surviving exposure to chemical nerve gas agents are at risk for permanent brain damage. What is needed is a nerve gas antidote with the following characteristics: (a) ability to rapidly degrade the OP, such as an OP hydrolase; (b) ability to cross the human BBB, so that OPs in the CNS are inactivated; this will minimize the permanent brain damage in individuals that survive exposure to chemical nerve gas agents. The most active OP hydrolase in human blood is paraoxonase (PON)-1. However, PON-1 does not cross the BBB. The delivery of large molecule therapeutics, such as PON-1, across the human BBB is now possible with BBB fusion protein technology developed by the Company. The present research project will genetically engineer a novel PON-1 fusion protein, which will be a bi-functional molecule. The new fusion protein will both contain high PON-1 OP hydrolase activity and be able to cross the human BBB via receptor-mediated transport. This will be accomplished by fusing human PON-1 to a BBB molecular Trojan horse that carries attached drugs from blood into brain via transport across the BBB. The new fusion protein will be engineered so that both the BBB transport activity and the PON-1 OP hydrolase activity will be preserved. Civilian, and military, populations are at risk for exposure to chemical nerve gas agents such as organophosphates (OPs). These compounds affect both the peripheral nervous system (PNS) and the central nervous system (CNS). The CNS is affected because the OPs are lipid-soluble small molecules that easily penetrate the brain, owing to transport across the blood-brain barrier (BBB). The present work will genetically engineer a novel OP hydrolase fusion protein that is able to cross the BBB in humans by receptor-mediated transport.


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: 2009 ( Subtotal = $677,113 )
2009	2009	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Trans-NIH Research Support	000	4	7/22/2009	NON-COMPETING CONTINUATION	$677,113
														Subtotal = $677,113

Issue Date FY: 2008 ( Subtotal = $495,075 )
2008	2008	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Trans-NIH Research Support	000	3	6/4/2008	NON-COMPETING CONTINUATION	$495,075
														Subtotal = $495,075

Issue Date FY: 2007 ( Subtotal = $480,657 )
2007	2007	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Trans-NIH Research Support	000	2	7/20/2007	NON-COMPETING CONTINUATION	$480,657
														Subtotal = $480,657

Issue Date FY: 2006 ( Subtotal = $298,276 )
2006	2006	ARMAGEN TECHNOLOGIES INC	11301 OLYMPIC BOULEVARD	LOS ANGELES	CA	90064	LOS ANGELES	USA	Trans-NIH Research Support	000	1	9/30/2006	NEW	$298,276
														Subtotal = $298,276

Grand Total All Awards = $1,951,121

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TARGETED PARAOXONASE FUSION PROTEIN AS A NEUROTHERAPEUTIC FOR NERVE GAS AGENTS

Award Number: U44NS057843

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/30/2006

PERIOD OF PERFORMANCE END DATE: 05/31/2010

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