Early Effect of Gene Therapy on a Direct Muscle Neurotization Model

ABSTRACT

Direct nerve-to-muscle neurotization has been the subject of both clinical and experimental studies. In this study, the authors report a new animal model to test the regenerative properties of a nerve (musculocutaneous) implanted in a muscle (biceps). They also report the early effects of the application at the implantation site of exogenously administered Brain Derived Nerve Factor (BDNF) and of endogenously produced BDNF, via the administration of an adenoviral construct with a tissue-specific promotor for muscle cells (AdRSV), and containing the BDNF gene. Evaluation included behavioral testing (grooming test), electrical stimulation, Western blot analysis of the distal implanted nerve to determine the presence of locally produced BDNF, and motor end-plate staining of the biceps muscle. At the early time point of 1 week following the musculocutaneous nerve to biceps muscle implantation, there was no increased production of recombinant BDNF at the distal implanted musculocutaneous nerve, as assessed by Western blot analysis. Therefore, there was no significant difference in the behavioral evaluation of the animals at 1 week; the Terzis grooming test showed no statistical difference among groups, but a trend toward better function for the BDNF and the high-dose AdRSV-BDNF groups, compared to the control groups. There was also no difference in the histologic appearance and number of the motor end-plates at the implantation site, compared to the controls. The electrical stimulation of the MC nerve did not produce statistically significant results among the experimental groups. In this direct nerve to muscle neurotization model, the application of AdRSV-BDNF at 3 × 10⁹ pfu/ul did not show enhanced production of BDNF at 1 week.

Nerve-to-muscle neurotization - BDNF - adenoviral construct

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