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Inducing Tolerance to Enzyme Replacement Therapy for Pompe Disease

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2012 / SBIR
Agency Tracking Number:
R43AI102454
Solicitation Year:
2012
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-123
Small Business Information
EPIVAX, INC.
146 CLIFFORD STREET PROVIDENCE, RI -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2012
Title: Inducing Tolerance to Enzyme Replacement Therapy for Pompe Disease
Agency: HHS
Contract: 1R43AI102454-01
Award Amount: $600,000.00
 

Abstract:

DESCRIPTION (provided by applicant): Inducing Tolerance to Enzyme Replacement Therapy for Pompe Disease Pompe disease is a lysosomal storage disorder caused by defects in the enzyme acid alpha-glucosidase (GAA) that leads to glycogen accumulation affectingheart and skeletal muscle. Enzyme-replacement therapy with recombinant human (rh)GAA saves the lives of children with Pompe disease. The prognosis for patients who have no circulating endogenous GAA (CRIM-negative Pompe disease) is markedly worse. The development of high titers of anti-rhGAA antibody and decreased effectiveness of replacement therapy often result in the death of CRIM-negative Pompe infants in the first year of life. We propose to evaluate the effect of natural tolerance-inducing peptides,Tregitopes, in a murine model of CRIM-negative Pompe disease. Tregitopes cause the expansion and activation of regulatory T cells, suppress inflammatory T cell responses and reduce humoral immune responses to co-administered proteins. In the plan outlinedhere, we will test Tregitopes co-delivered with GAA epitopes, as a tolerance-inducing (1) Prophylactic therapy or (2) Therapeutic treatment of ongoing anti-GAA immune responses. We will evaluate an AAV-vector for Tregitope-GAA epitope delivery. The programwill establish proof-of-principle that will lead to further studies in Phase II. Even a moderate degree of success with the protocol developed here may improve the lives of CRIM-negative babies and could be applied to other enzyme replacement therapies towhich ADA have been induced. An experienced team will carry out the program, including Richard Garman who has extensive experience with the Pompe mouse model, Annie De Groot, a well-established T cell immunologist, Leslie Cousens, Ph.D. expert in Tregitope immunomodulation studies, Tim Messitt, Ph.D. molecular biologist and Federico Mingozzi Ph.D., AAV expert, who will co-develop the Tregitope-GAA AAV vector. PUBLIC HEALTH RELEVANCE: We propose to evaluate the effect of natural tolerance-inducing peptides, Tregitopes (T regulatory cell epitopes), to induce long-lasting and specific tolerance to enzyme replacement therapy in a murine model of Pompe disease. Proof of principle for Tregitopes in treating anti-drug antibody responses in the context of Pompedisease will have immediate impact on the field of enzyme replacement therapy and could lead to accelerated adaptation of Tregitope therapy in the treatment of these children.

Principal Investigator:

Anne S. Degroot
401-272-2123
annied@epivax.com

Business Contact:

Christine Boyle
401-272-2123
christine_boyle@epivax.com
Small Business Information at Submission:

EPIVAX, INC.
146 CLIFFORD STREET PROVIDENCE, RI -

EIN/Tax ID: 105049938
DUNS: N/A
Number of Employees: N/A
Woman-Owned: Yes
Minority-Owned: No
HUBZone-Owned: No