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Musculoskeletal Tissue Degeneration in the Setting of Prosthetic Joint Infection

Award Number: R21AR088425
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Musculoskeletal Tissue Degeneration in the Setting of Prosthetic Joint Infection - PROJECT SUMMARY/ABSTRACT With the increasing demand of total joint replacement procedures (more than 1 million per year by 2030) coupled with the continuing rise in the incidence of antibiotic-resistance, prosthetic joint infection (PJI) is a critical issue in orthopaedics. Persistent PJI is debilitating and results in osteolysis, disability, and mortality. While research has focused on eradicating the infection, limited attention has focused on characterizing and treating the pathology of the musculoskeletal tissue. Our long-term goal is to understand the etiology of degeneration in tissues affected by PJI and to identify new therapeutic targets for improved treatments. The objective of this proposal is to investigate the musculoskeletal degenerative pathway in PJI and to assess a novel calcium channel blocker – ELP-004, which is a transient receptor potential canonical (TRPC) channel inhibitor – to improve the outcomes of bone and skeletal muscle with PJI. We will test the hypothesis that PJI triggers TRPC- mediated osteolysis and muscle degeneration and that inhibition of TRPC will improve these outcomes. Two specific aims will be conducted in an established in vivo PJI preclinical model: (Aim 1) Evaluate the efficacy of a TRPC channel inhibitor to maintain bone integrity during simulated PJI. We hypothesize that in a preclinical Sprague Dawley rat model of PJI, decreases in bone mineral density will be offset with oral gavage treatment of ELP-004. Resulting anatomical and cellular bone changes will be assessed by micro-CT, tartrate-resistant acid phosphatase staining, and bone remodeling relevant gene expression (NFATc1 and related genes) compared to vehicle control treatment. These data will result in new insights for osteolysis and evaluation of TRPC channel inhibition as a therapeutic strategy. (Aim 2) Establish the ability of TRPC channel inhibition to attenuate PJI- induced muscle degeneration. We hypothesize that in our preclinical PJI rat model, the prevalence of muscle fiber degeneration, fiber type transformation, and weakness will increase – while ELP-004 administration will counter these pathological changes. Methods will consist of immunohistochemistry, ELISA, qPCR, and measurement of contractile properties ex vivo. This aim will provide evidence for TRPC-mediated degeneration of skeletal muscle in PJI. Achieving these aims will provide the new data necessary for proposing an NIH R01 grant submission to assess degenerative pathways and performance testing of this hypothesis in patient tissue samples. These findings will contribute to insights of changes in bone and skeletal muscle pathology in the presence of PJI and evaluate a novel therapeutic approach. In addition, these research findings will have implications for other common implant-related infections.


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 = $331,959 )
2026	2026	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/18/2026	NEW	$331,959
														Subtotal = $331,959

Grand Total All Awards = $331,959

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Musculoskeletal Tissue Degeneration in the Setting of Prosthetic Joint Infection

Award Number: R21AR088425

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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