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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Doxil-induced chemomyectomy: effectiveness for permanent removal of orbicularis oculi muscle in monkey eyelid.

PURPOSE. To test the safety and effectiveness of Doxil chemomyectomy in monkey eyelids using treatment schedules and doses similar to those proposed for the human blepharospasm patients in Phase I and II trials. METHODS. Bupivacaine/hyaluronidase and Doxil were injected sequentially into the eyelids of five Cynomolgus monkeys. Eyelids received 1, 2, or 3 sets of injections. The monkeys were euthanatized at a minimum of 2 months and a maximum of 12 months after the final treatment. The eyelids were prepared for histologic examination, and muscle fiber loss was quantified. RESULTS. All Doxil injections resulted in a significant loss of myofibers. No bruising, ulceration, or other skin injuries occurred, even after a third injection regimen within a single treated eyelid. Two-day preinjury with a bupivacaine/hyaluronidase mixture had a significant adjuvant effect. CONCLUSIONS. Doxil chemomyectomy is an effective protocol to permanently remove muscle from injected eyelids in nonhuman primates. Serial injections over the course of several months using the preinjury protocol combined with Doxil treatment significantly increased Doxil's myotoxic effects. Additionally, the injection of the liposome-encapsulated form of doxorubicin did not result in skin injury or ulceration. Species differences demonstrated the importance of testing these drugs in nonhuman primates. Thus, repeated doses of Doxil may prove to be as clinically effective as free doxorubicin injections in reducing muscle spasms in blepharospasm patients but with increased safety to the skin and tissue around the injection site.[1]


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