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Dual Targeting of Inflammation and Fibrosis in DMD with CAR-T Therapy

Award Number: R21AR087645
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/05/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Dual Targeting of Inflammation and Fibrosis in DMD with CAR-T Therapy - Abstract: Chronic inflammation and fibrosis are hallmark pathologies of Duchenne Muscular Dystrophy (DMD), yet current therapies focus on restoring dystrophin in muscle cells and largely overlook the pathological microenvironment. This niche—sustained by pro-inflammatory macrophages and fibrogenic fibro-adipogenic progenitors (FAPs)—impairs regeneration and reduces therapeutic efficacy. Existing gene therapies perform poorly in fibrotic muscle and require high doses that have caused toxicity and patient deaths. To address this critical therapeutic gap, we propose a first-in-class chimeric antigen receptor T cell (CAR-T) therapy for DMD that dually targets both inflammatory macrophages and fibrogenic FAPs to reprogram the dystrophic niche. While CAR-T therapies have revolutionized cancer treatment, they have not been applied to DMD or regenerative medicine. Supported by preliminary data, our goal is to develop a CAR-T cell therapy that can eliminate pro-inflammatory macrophages and fibrogenic FAPs, restore muscle stem cell (MuSC) regenerative potential, and improve both limb and diaphragm function in pre-clinical murine models of DMD. Specifically, we will: (Aim 1) Evaluate the effect of CAR-T therapy on inflammation and fibrosis; (Aim 2) Assess its impact on muscle regeneration and function. This paradigm-shifting approach addresses a major unmet need by targeting the inflamed-fibrotic niche and may enhance the effectiveness of current gene and cell therapies. If successful, it will establish a new therapeutic framework for DMD and other muscle diseases marked by chronic inflammation and fibrosis.


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 = $377,506 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/9/2026	NEW	$377,506
														Subtotal = $377,506

Grand Total All Awards = $377,506

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Dual Targeting of Inflammation and Fibrosis in DMD with CAR-T Therapy

Award Number: R21AR087645

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/05/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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