Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

IDURONIDASE REPLACEMENT THERAPY OF THE BRAIN IN HURLER'S SYNDROME

Award Number: U44NS064602
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: 06/15/2009
PERIOD OF PERFORMANCE END DATE: 05/31/2012

Group Awards By:

View Award Description

IDURONIDASE REPLACEMENT THERAPY OF THE BRAIN IN HURLER'S SYNDROME - DESCRIPTION (provided by applicant): Abstract There are over 40 lysosomal storage disorders, and most of these diseases affect adversely the central nervous system (CNS). The mainstay of treatment is enzyme replacement therapy (ERT). However, ERT is not effective for the brain, because the enzymes do not cross the brain capillary wall, which forms the blood-brain barrier (BBB) in vivo. Without treatment of the CNS, the young patients are destined to progressive neurodegeneration and death. The limiting factor in the future treatment of these diseases is the transport of the enzyme across the BBB. Bypass of the BBB with direct injection into the brain is not effective, because only a small part of the brain is treated with a trans-cranial delivery system. Conversely, virtually all cells of the brain can be treated with a trans-vascular delivery system that enables the enzyme to cross the BBB following intravenous administration. A new approach to the BBB delivery of large molecules such as enzymes is the molecular Trojan horse technology. A bi-functional fusion protein is produced with genetic engineering, wherein the missing recombinant enzyme is fused to a BBB molecular Trojan horse. The latter is a genetically engineered protein that is able to cross the human BBB by receptor- mediated transcytosis on endogenous BBB peptide transport systems. Pre-clinical studies show that a large enzyme with a molecular weight >100,000 Daltons, can be delivered to brain via transport across the BBB, following attachment to a BBB receptor-specific Trojan horse. The present work will produce a novel fusion gene encoding human iduronidase and a genetically engineered molecular Trojan horse, which will allow the production of the corresponding fusion protein, AGT-181. This new fusion protein will be a new treatment of the brain in Hurler's syndrome. The aims of this work are to manufacture bioreactor-generated AGT-181, perform the GLP pharmacology-toxicology of this new drug, examine the tissue cross reactivity of AGT-181, and to prepare and file an IND to the FDA for the treatment of the brain in Hurler's syndrome. PUBLIC HEALTH RELEVANCE: Project Narrative Lysosomal storage disorders are serious inborn errors of metabolism, and about 75% of the ~40 lysosomal storage disorders affect the brain. The mainstay of treatment is Enzyme Replacement Therapy (ERT). However, ERT is ineffective in the brain, because the enzymes do not cross the blood-brain barrier (BBB). The present work will produce a novel recombinant fusion protein that is able to both (a) bind a human BBB receptor to trigger transport into the brain, and (b) retain high lysosomal enzyme activity. This novel drug, designated AGT-181, will be new treatment for the brain in Hurler's syndrome.


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: 2011 ( Subtotal = $977,882 )
2011	2011	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	6/10/2011	NON-COMPETING CONTINUATION	$79,608
2011	2011	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/6/2011	NON-COMPETING CONTINUATION	$898,274
														Subtotal = $977,882

Issue Date FY: 2010 ( Subtotal = $982,874 )
2010	2010	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/29/2010	NON-COMPETING CONTINUATION	$982,874
														Subtotal = $982,874

Issue Date FY: 2009 ( Subtotal = $980,092 )
2009	2009	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/5/2009	COMPETING CONTINUATION	$980,092
														Subtotal = $980,092

Grand Total All Awards = $2,940,848

Top

All Categories

About

Search

Reports

Data Submission

Award Information

IDURONIDASE REPLACEMENT THERAPY OF THE BRAIN IN HURLER'S SYNDROME

Award Number: U44NS064602

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: 06/15/2009

PERIOD OF PERFORMANCE END DATE: 05/31/2012

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer