Tacrolimus for Myasthenia Gravis

Brief Alert

Source: Evoli A, et al. Successful treatment of myasthenia gravis with tacrolimus. Muscle Nerve. 2002;25:111-114.

Immunosuppression for the treatment of myasthenia gravis may be achieved by several agents, including prednisone, azathioprine, cyclosporine A, or mycophenolate mofetil (CellCept). This case report indicates that the new immunosuppressant, tacrolimus (FK-506), may also be beneficial.

A 56-year-old diabetic man developed myasthenia during interferon alpha 2b (Intron) therapy for hepatitis C. Diagnosis was confirmed by a decremental response on repetitive nerve stimulation testing and elevated acetylcholine receptor antibody titers. Pyridostigmine proved beneficial. Deterioration of myasthenia occurred 4 months later and cyclosporine was initiated. Prednisone and azathioprine were contraindicated due to the diabetes and hepatitis. Thymectomy followed 2 years later. Worsening renal function resulted in discontinuation of cyclosporine, and tacrolimus 2 mg b.i.d. (approximately 0.05 mg/kg) was begun for control of myasthenic symptoms. Improvement of myasthenia was seen within 2 weeks. One month later only arm fatigability and mild eye closure weakness was present. At last follow-up 15 months later, the patient was in remission.

Commentary

Tacrolimus (FK506, Prograf) was approved for liver transplantation in 1994, for renal transplantation in 1997, and is also used for heart, lung, and pancreas transplants. Together with cyclosporine A and rapamycin (FKBP-12, sirolimus), it is one of a group of immunophilin-binding agents. Immunophilins are cytosolic isomerases which activate T cells and, by binding these molecules, inhibition of T cell specific kinases and phosphatases is achieved. Like cyclosporine, the target of tacrolimus is calcineurin, a calcium-calmodulin regulated, serine-threonine protein phosphatase which regulates the nuclear importation of a transcription factor, NF-AT (nuclear factors of activated T cells). NF-AT is required for cytokine gene expression and, in its absence, T cell activation is inhibited. Tacrolimus’ safety profile appears similar to cyclosporine with respect to renal dysfunction, hyperglycemia, hyperkalemia, or hypomagnesemia. Hypercholesterolemia, hypertension, hirsutism, and gingival hyperplasia are less common. Favorable reviews of tacrolimus to date ensure that its use in neurological conditions is likely to increase. —Michael Rubin, MD. Dr. Rubin, Associate Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.