SP38. Intramuscular Collagenase Injection as a Treatment for Chronic Denervation-induced Muscle Fibrosis

PURPOSE: While collagen in healthy muscle serves as a structural scaffold, excessive collagen deposition in denervation-induced fibrosis disorganizes tissue architecture and disrupts the regeneration of myofibers, axons, and blood vessels. It also affects the elastic properties and contractility of the muscle, leading to progressive stiffness, contractures, and reduced range of motion. Collagenase has shown promising results in several animal models of solid organ and soft-tissue fibrosis and is currently FDA-approved for treating Dupuytren’s contracture, Peyronie’s disease, and cellulite. This study investigates the safety and efficacy of intramuscular collagenase injection as a treatment for chronic denervation-induced muscle fibrosis. METHODS: Twenty-one adult Lewis rats (male and female) were randomly assigned to three groups: experimental, positive control, and negative control. The experimental and positive control groups underwent median nerve transection, while the negative control group had sham surgery. After 16 weeks of denervation, all groups underwent ulnar-to-median nerve transfer. At 32 weeks post-transfer, the experimental group received 150 U of collagenase in 100 μl saline; controls received 100 μl saline. All animals underwent biweekly grip-strength testing, and ultrasound and shear-wave elastography were performed before and 2 weeks after the injections. Muscle composition and texture were assessed using the gray-level co-occurrence matrix (GLCM) on ultrasound B-mode images. Shear-wave velocity was measured and compared between groups. Statistical analysis was performed using R version 4.2.3. RESULTS: No serious adverse events were observed following injections. GLCM analysis showed higher angular second moment (ASM) and lower entropy values in post-injection B-mode images in the experimental group, suggesting reduced tissue heterogeneity (ASM, pre-injection: 0.004 ± 0.001 vs post-injection: 0.01 ± 0.001; entropy, pre-injection: 5.57 ± 0.18 vs post-injection: 5.08 ± 0.29; both p < 0.0001). Shear-wave elastography showed decreased muscle stiffness (pre-injection: 3.50 ± 0.22 m/s; post-injection: 2.84 ± 0.26 m/s; p < 0.0001). By week 40 (8 weeks post-injection), experimental animals showed a significant increase in grip strength compared to pre-injection levels (pre-injection: 2.38 ± 0.50 N; post-injection: 3.33 ± 0.75 N; paired t-test p = 0.0008). CONCLUSION: Our findings demonstrate preserved grip strength, decreased tissue heterogeneity, and reduced muscle stiffness following intramuscular collagenase injection. Histological assessments are currently underway to fully understand the safety and efficacy of collagenase as a treatment for chronic denervation-induced muscle fibrosis.