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

TRPC6 inhibition therapy to rescue cardiac muscle dysfunction in muscular dystrophy

Award Number: R00HL155840
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/18/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

TRPC6 inhibition therapy to rescue cardiac muscle dysfunction in muscular dystrophy - This proposal tests the efficacy and mechanisms by which a recently developed, bioavailable, selective small-molecule inhibitor of Transient Receptor Potential Canonical 6 (TRPC6) ameliorates cardiac and skeletal myopathy in Duchenne muscular dystrophy (DMD). This research fulfills the candidate’s long-term goals of advancing novel therapies for dystrophic cardiomyopathy and applying mechanosensitive signaling assays in mice and engineered heart tissues (EHT) to study disease. DMD results from a loss of dystrophin, inducing profound progressive muscle weakness, spinal deformities, fibrosis, heart failure, and early mortality. TRPC6 is a mechanosensitive, non-voltage gated cation channel expressed in muscle cells that is hyper-activated in DMD, mediating excessive mechanical stress-induced force/Ca2+ responses, arrhythmias, cardiac dysfunction, and muscle fibrosis. During the candidate’s postdoctoral training, he led projects assessing the impact of blocking TRPC6 genetically and pharmacologically in models of cardiac fibrosis. Preliminary data in DMD show genetic or pharmacological TRPC6 inhibition prolongs lifespan in severe DMD models by 2-3 fold, ameliorating fibrosis and associated pathology, and improving heart and skeletal muscle function. The candidate first reported on the TRPC6 drug inhibitor (BI 749327) in 2019, and its clinical derivatives are now in human trials for lung and renal disease. In this proposal, the candidate addresses key questions whose answers will importantly inform future DMD translational efforts, and organized into three aims. Aim 1 tests the efficacy of chronic TRPC6 inhibition by BI 749327 to prevent and reverse DMD skeletal and cardiac muscle dysfunction, histopathology, and TRPC6-NFAT, pro-fibrotic and inflammatory signaling. Cell-type expression is analyzed by single-cell RNAseq to identify how subpopulations of cardiac cells that express TRPC6 (fibroblasts, vascular, and myocytes) are impacted by the treatment. Aim 2 tests the capacity of chronic TRPC6 suppression to restore mechanical activation-induced defects in force and calcium in isolated DMD mouse cardiomyocytes, and to obviate effects of membrane sealants and other mechanosensitive-activated pathways. I will further test the role of TRPC6 pathobiology in a novel human DMD EHT model of mechanosensitive activation using the same mechanical stimuli as in mouse cardiomyocytes. Aim 3 tests the efficacy of micro-dystrophin (ȝDys) gene therapy to treat TRPC6 pathobiology in the recently developed D2 mdx DMD mouse model or the combination of ȝDys with BI


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: 2026 ( Subtotal = $249,000 )
2026	2026	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	000	5	4/17/2026	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2025 ( Subtotal = $249,000 )
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	000	4	2/24/2025	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2024 ( Subtotal = $258,400 )
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	001	3	5/10/2024	EXTENSION WITH OR WITHOUT FUNDS	$9,400
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	000	3	3/18/2024	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $258,400

Grand Total All Awards = $756,400

Top

All Categories

About

Search

Reports

Data Submission

Award Information

TRPC6 inhibition therapy to rescue cardiac muscle dysfunction in muscular dystrophy

Award Number: R00HL155840

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/18/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer