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Understanding regulation of pediatric regenerative myogenesis and its implication for muscle disease

Award Number: R01NS136349
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Understanding regulation of pediatric regenerative myogenesis and its implication for muscle disease - ABSTRACT The maintenance of healthy skeletal muscle and its regeneration following acute injury involves precise regulation of the resident stem cell response by the surrounding muscle niche. Pediatric muscles respond quickly and are more proficient at regenerating from injury. The decline in regenerative capacity of geriatric muscle is widely studied, where the muscle niche is recognized to be a key contributor in the decline of the regenerative capacity of the muscle stem cells. However, the factors that support efficient regenerative capacity of pediatric muscle are less understood. The limited work in this area has focused on ex vivo examination of the intrinsic myogenic capacity of muscle stem cells but fails to capture the role of the muscle niche in driving pediatric muscle regeneration. An understanding of this is required as multiple degenerative muscle diseases, such as DMD, manifest from early childhood, where therapies that can maintain or further enhance pediatric muscle regenerative capacity can ameliorate the impact of this disease. The work proposed here aims to address this knowledge gap by building on our preliminary studies implicating the interplay of immune and stromal factors in the muscle niche for efficient regenerative myogenesis of pediatric muscle (Aim 1) and identify how these interactions are impaired in dystrophic that attenuates regenerative myogenesis and how targeting this holds therapeutic potential (Aim 2). We will make use of a combination of single-cell and spatial RNA transcriptomic analyses together with various DMD mouse models and patient samples to examine this process and validate our findings. Through use of these complimentary approaches the work here will provide basic insights into the regulation of healthy pediatric regenerative myogenesis with broad applicability to DMD and other pediatric onset degenerative muscle wasting diseases.


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: 2025 ( Subtotal = $692,292 )
2025	2025	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/28/2025	NEW	$692,292
														Subtotal = $692,292

Grand Total All Awards = $692,292

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Understanding regulation of pediatric regenerative myogenesis and its implication for muscle disease

Award Number: R01NS136349

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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