Recovery of Chronically Denervated Muscle Enhanced with Follistatin Treatment
Jonathan Isaacs, MD1; Satya Mallu, MD1; Mark Feger, PhD2; Gaurangkumar Patel, BS2
1Division of Hand Surgery, Department of Orthopaedic Surgery, Virginia Commonwealth University, Richmond, VA, 2Virginia Commonwealth University, Richmond, VA
Introduction: Poor functional recovery following major peripheral nerve injury is largely due to the progressive catabolic process (denervation atrophy) affecting muscle fibers. Follistatin is a glycoprotein that blocks the muscle growth inhibiting peptide myostatin and also possesses remarkable independent muscle stimulating properties. We hypothesized that the administration of follistatin to rodent muscles subjected to prolonged but temporary denervation (3 or 6 months) would improve final muscle recovery and function.
Materials and methods: One hundred forty-four (three-month old female) Sprague-Dawley rats were divided into 8 groups comprising animal muscles with or without temporary denervation and subsequent repair (3 or 6 months) and with or without follistatin treatment (delivered via Adenovirus viral vector containing recombinant DNA or direct delivery of recombinant protein via subcutaneous osmotic pumps). After final recovery, muscle weight and force were recorded and statistically compared between groups with an alpha level of .05.
Results: For 3-month denervation groups, there was no improvement in muscle weight or force generation following either protein or recombinant DNA treatment. For 6-month group, virus administration resulted in higher final muscle weights in both denervation and sham denervation groups. Protein treatment resulted in greater muscle force generation in the denervation group.
Six month chronically denervated muscle showed modest improvements in muscle mass and strength recovery following follistatin treatment. The effect was not consistent and further study will be necessary to elucidate any future role of this novel treatment strategy.
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