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Metachromatic Leukodystrophy Enzyme Drug Development

Award Number: R44HD074272
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2012
PERIOD OF PERFORMANCE END DATE: 03/31/2015

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Metachromatic Leukodystrophy Enzyme Drug Development - DESCRIPTION (provided by applicant): Metachromatic Leukodystrophy or MLD, is a genetic disease that affects the lysosomal enzyme, arylsulfatase A (ASA). People born with MLD develop extensive lysosomal storage product accumulation in tissues, including the brain. Children with MLD develop multiple brain disorders including mental retardation and hydrocephalus early in life. The current therapy in clinical trials for MLD is Enzyme Replacement Therapy (ERT) with the recombinant human enzyme, ASA. However, ERT does not treat the brain of MLD, because ASA does not cross the blood-brain barrier (BBB). The present work will continue work on the development of a new treatment of the brain of MLD, which is a genetically engineered IgG-enzyme fusion protein. The ASA enzyme is fused to a BBB molecular Trojan horse, which is a genetically engineered peptidomimetic monoclonal antibody (MAb) against an endogenous BBB peptide receptor, the human insulin receptor (HIR). The human ASA is fused to the heavy chain of the HIRMAb to create a new biological entity, the HIRMAb-ASA fusion protein named AGT-183. Phase I studies show the HIRMAb-ASA fusion protein could be engineered and expressed by stably transfected host cells. The fusion protein retained high affinity binding to the HIR, retained high ASA enzyme activity, was triaged to the lysosomal compartment of MLD fibroblasts, and rapidly penetrated the BBB in rhesus monkeys after intravenous administration. The proposed phase II work will develop a manufacturing plan that can be replicated for future GMP manufacturing. The AGT-183 produced in phase II will be evaluated for safety, toxicology and pharmacokinetics in Rhesus monkeys. The completion of this work will enable entry of the AGT-183 drug development program into GLP toxicology and GMP manufacturing required for submission of an IND to begin treatment of the brain in patients with MLD.


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 = $583,336 )
2014	2014	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Child Health and Human Development Extramural Research	000	3	4/4/2014	NON-COMPETING CONTINUATION	$583,336
														Subtotal = $583,336

Issue Date FY: 2013 ( Subtotal = $416,309 )
2013	2013	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Child Health and Human Development Extramural Research	000	2	3/29/2013	COMPETING CONTINUATION	$416,309
														Subtotal = $416,309

Grand Total All Awards = $999,645

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Metachromatic Leukodystrophy Enzyme Drug Development

Award Number: R44HD074272

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2012

PERIOD OF PERFORMANCE END DATE: 03/31/2015

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