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Metachromatic Leukodystrophy Enzyme Drug Development

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2012 / SBIR
Agency Tracking Number:
R43HD074272
Solicitation Year:
2012
Solicitation Topic Code:
NICHD
Solicitation Number:
PA11-096
Small Business Information
ARMAGEN TECHNOLOGIES, INC.
26679 Agoura Rd. #100 Calabasas, CA -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2012
Title: Metachromatic Leukodystrophy Enzyme Drug Development
Agency: HHS
Contract: 1R43HD074272-01
Award Amount: $156,555.00
 

Abstract:

DESCRIPTION (provided by applicant): Metachromatic leukodystrophy (MLD) is an genetic disease caused by mutations in the gene encoding the lysosomal enzyme, arylsulfatase A (ASA). Symptoms including neurodegeneration and mental retardation appear during infancy or childhood; and early death can occur due to organ damage in the brain. Enzyme replacement therapy (ERT) cannot treat the brain, since recombinant ASA does not cross the blood-brain barrier (BBB). Accordingly, clinical trials of children with MLD and recombinant ASA have been abandoned. The present work will re-engineer human ASA to enable transport across the BBB using a molecular Trojan horse technology. A molecular Trojan horse is a genetically engineered peptidomimetic monoclonal antibody (MAb)against an endogenous BBB peptide receptor, such as the human insulin receptor (HIR). The human ASA is fused to the heavy chain of the HIRMAb to create a new chemical entity, called the HIRMAb-ASA fusion protein. Feasibility studies with the HIRMAb-ASA fusion protein were enabled following the cloning of a high producing, stably transfected host cell line. The HIRMAb-ASA fusion protein retains high ASA enzyme activity and high binding to the HIR. This phase I SBIR work will further validate the pharmacologic activity of the HIRMAb-ASA fusion protein in MLD fibroblasts, using ASA enzyme activity assays and confocal microscopy. The HIRMAb-ASA fusion protein penetration of the BBB in vivo will be confirmed in the Rhesus monkey. This work provides the rationalefor future phase II studies that provide the bridge to subsequent GMP/GLP work that supports an IND for treatment of MLD with the HIRMAb-ASA fusion protein. PUBLIC HEALTH RELEVANCE: Metachromatic leukodystrophy (MLD) is an genetic disease caused by mutations in the gene encoding the lysosomal enzyme, arylsulfatase A (ASA). Enzyme replacement therapy cannot treat the brain, since recombinant ASA does not cross the blood-brain barrier. The present work will re- engineer human ASA to enable transportacross the BBB using a molecular Trojan horse technology.

Principal Investigator:

Ka-wai Hui
310-917-1275
ehui@armagen.com

Business Contact:

Ruben J. Boado
310-917-1275
rboado@armagen.com
Small Business Information at Submission:

ARMAGEN TECHNOLOGIES, INC.
26679 Agoura Rd. Suite 100 Calabasas, CA -

EIN/Tax ID: 177062671
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No