Friday, April 26, 2024 4/26/2024

Center for Research Translation of Systemic Exon-skipping in Muscular Dystrophy

Award Number: P50AR060836
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

DESCRIPTION (provided by applicant): The identification of the Duchenne muscular dystrophy gene and protein in the late 1980's led to high hopes of rapid translation to rational therapeutics. Early reports of delivering new functional genes to mouse model muscle via gene therapy and stem cell therapy fueled this hope. However, these same studies illuminated the very high hurdles facing human applications. Insufficient therapeutic material (cells, viral vectors), challenges in systemic delivery, and immunological hurdles all remain barriers to demonstration of efficacy of exogenous gene delivery. An alternative approach Is to repair the patient's own gene, and two innovative small molecule approaches have emerged as front-line experimental therapeutics: stop codon read through, and exon skipping. Both approaches are In human clinical trials, and aim to coax dystrophin protein production from mutant genes. In the clinically severe dog model of DMD, the exon-skipping approach is the first therapeutic method that showed improvement of multiple functional outcomes. The proposed CORT is focusing on exon-skipping, the approach that holds promise for the majority of DMD patients. Exon skipping as a drug development program Is highly complex. Patients have different mutations, and drugs must be customized to groups of patients sharing overlapping deletions. Given the high cost of drug development, there is an emerging consensus that exon skipping should achieve drug approval 'as a class'. Three exon-specific drugs should be systematically studied, showing safety and efficacy. The procedures and rules optimized for these three drugs can then be generalized to other, less commonly applicable exon- specific drugs, with reduced regulatory hurdles. The goal of this CORT is to systematically study the three most commonly applicable exon-specific drugs (exons 45,51.53). Project 1 will determine the splicing fidelity and protein function corresponding to the In-frame transcripts generated by the drugs. Project 2 will optimize sequence selection for each exon using multiple experimental systems, and test optimized drugs in a 1 yr pre-clinical efficacy study. Project 3 will carry out the first natural history study of the targeted in-frame deletions (Becker muscular dystrophy); this will permit some prediction of clinical efficacy from production of the relevant semi-functional dystrophin proteins. These three Projects draw upon two research cores: Core B (In vitro and In vivo functional assays), and Core C (Molecular diagnostics and cell banking).


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: 2019 ( Subtotal = -$312,399 )
2019	2015	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	12/31/2018	NON-COMPETING CONTINUATION	-$312,399
														Subtotal = -$312,399

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2015	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	8/3/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $1,532,326 )
2015	2015	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	9/17/2015	NON-COMPETING CONTINUATION	$1,532,326
														Subtotal = $1,532,326

Issue Date FY: 2014 ( Subtotal = $1,542,768 )
2014	2014	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	8/25/2014	NON-COMPETING CONTINUATION	$1,542,768
														Subtotal = $1,542,768

Issue Date FY: 2013 ( Subtotal = $1,469,599 )
2013	2013	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	9/12/2013	NON-COMPETING CONTINUATION	$1,469,599
														Subtotal = $1,469,599

Issue Date FY: 2012 ( Subtotal = $1,570,974 )
2012	2012	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	9/12/2012	NON-COMPETING CONTINUATION	$1,570,974
														Subtotal = $1,570,974

Issue Date FY: 2011 ( Subtotal = $1,674,363 )
2011	2011	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/9/2011	NEW	$1,674,363
														Subtotal = $1,674,363

Grand Total All Awards = $7,477,631

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Center for Research Translation of Systemic Exon-skipping in Muscular Dystrophy

Award Number: P50AR060836

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer