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Inducing Tolerance to Enzyme Replacement Therapy for Pompe Disease

Award Number: R43AI102454
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2012
PERIOD OF PERFORMANCE END DATE: 08/31/2016

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Inducing Tolerance to Enzyme Replacement Therapy for Pompe Disease - 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 affecting heart 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 outlined here, 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 program will 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 to which 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.


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: 2017 ( Subtotal = $0 )
2017	2013	EPIVAX, INC.	146 CLIFFORD ST STE 3	PROVIDENCE	RI	02903	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	2	1/31/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2013	EPIVAX, INC	146 CLIFFORD STREET	PROVIDENCE	RI	02903	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	2	8/31/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $300,000 )
2013	2013	EPIVAX, INC	146 CLIFFORD STREET	PROVIDENCE	RI	02903	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	2	7/22/2013	NON-COMPETING CONTINUATION	$300,000
														Subtotal = $300,000

Issue Date FY: 2012 ( Subtotal = $300,000 )
2012	2012	EPIVAX, INC	146 CLIFFORD STREET	PROVIDENCE	RI	02903	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	1	8/31/2012	NEW	$300,000
														Subtotal = $300,000

Grand Total All Awards = $600,000

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Inducing Tolerance to Enzyme Replacement Therapy for Pompe Disease

Award Number: R43AI102454

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2012

PERIOD OF PERFORMANCE END DATE: 08/31/2016

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