Long-term Reduction of Muscle Function Through Chemomyectomy and Inhibition of Regeneration

Intramuscular injection of botulinum toxin has revolutionized the management of benign essential blepharospasm, other involuntary movement disorders, and is currently employed for cosmetic purposes. The major drawback to botulinum therapy in these treatments is that the paralytic effect is temporary and re-injection must occur every few months. Axonal sprouting has been proposed as the major reason for such return of function to the muscles paralyzed by botulinum toxin and its periodic elimination requires multiple injections which are both a physical and financial burden on the patient suffering from these conditions. We have searched for a,nalternative to botulinum toxin that will provide more long-lasting relief. We have shown (unpublished) that the protein tyrosine kinase inhibitor genistein blocks both proliferation and differentiation of skeletal muscle satellite cells and we hypothesize that in combination with the myotoxic anesthetic marcaine (bupivicaine), genistein will greatly prolong therapeutic reduction of muscle function. Marcaine by itself causes reduction of function by lysis of muscle fibers; muscle stem cells (satellite cells) subsequently proliferate and regenerate the damaged tissue. We intend to inject marcaine into experimental animal orbicularis oculi muscles to cause degeneration and to deliver the tyrosine kinase inhibitor in slow-release form to inhibit regeneration of muscle fibers. We predict that this novel treatment will result in long-lasting, perhaps permanent reduction of unwanted muscle activity. In the clinical setting, reduction or elimination of the need for further treatments during a lifelong disease would result in substantial financial advantage to individuals and the health care system at large and result in a substantial reduction of patient discomfort. .