Follistatin Concentrations following Two Novel Recombinant Delivery Methods in Chronically Denervated Muscle
Satya Mallu, MD; Mark Feger, PhD; Gaurangkumar Patel, BS; Mary Shall, PhD; Jonathan Isaacs, MD
Division of Hand Surgery, Department of Orthopaedic Surgery, Virginia Commonwealth University, Richmond, VA
Introduction:
Partial but functionally unsatisfactory motor recovery following major peripheral nerve injury and repair is common. 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 recombinant follistatin to rodent muscles subjected to prolonged but temporary denervation (3 or 6 months) would result in increased follistatin protein concentrations and thus an anabolic environment during muscle recovery following nerve repair.
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, follistatin protein levels were quantified via enzyme-linked immunosorbent assays and statistically compared between groups with an alpha level of .05.
Results:
For 3-month denervation groups, there were significantly higher follistatin protein concentrations following recombinant DNA treatment compared to direct protein delivery. For 6-month group, recombinant DNA treatment resulted in significantly higher follistatin protein concentrations in both denervation and sham denervation groups.
Conclusion:
We successfully delivered recombinant follistatin protein to prolonged but temporarily denervated muscle in a validated rodent model for peripheral nerve injury. Recombinant DNA delivery via Adenovirus viral vector resulted in the highest follistatin protein concentrations at 3 and 6 months. The protein concentrations for each delivery method were not consistent across treatment groups and further study will be necessary to elucidate any future role of this novel treatment strategy and to correlate protein concentration with functional muscle recovery.
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