University of Oxford

Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis.

Vincent A. Leiti MI.

Neurosciences Group, Weatherall Institute of Molecular Medicine and Department of Clinical Neurology, University of Oxford, Oxford, UK. Angela.vincent@imm.ox.ac.uk PURPOSE OF REVIEW: Some of the 20% of myasthenia gravis patients who do not have antibodies to acetylcholine receptors (AChRs) have antibodies to muscle specific kinase (MuSK), but a full under-standing of their frequency, the associated clinical phenotype and the mechanisms of action of the antibodies has not yet been achieved. Moreover, some patients do not respond well to conventional corti-costeroid therapy. Here we review recent clinical and experimental studies on MuSK antibody associated myasthenia gravis, and summarize the results of newer treatments for myasthenia gravis. RECENT FINDINGS: MuSK antibodies are found in a variable proportion of AChR antibody negative myasthenia gravis patients who are often, but not exclusively, young adult females, with bulbar, neck, or respiratory muscle weakness. The thymus histology is normal or only very mildly abnormal. Surprisingly, limb or intercostal muscle biopsies exhibit no reduction in AChR numbers or complement deposition. However, patients without AChR or MuSK antibodies appear to be similar to those with AChR antibodies and may have low-affinity AChR antibodies. A variety of treatments, often intended to enable corticosteroid doses to be reduced, have been used in all types of myasthenia gravis with some success, but they have not been subjected to randomized clinical trials. SUMMARY: MuSK antibodies define a form of myasthenia gravis that can be difficult to diagnose, can be life threatening and may require additional treatments. An improved AChR antibody assay may be helpful in patients without AChR or MuSK antibodies. Clinical trials of drugs in other neuroimmu-nological diseases may help to guide the treatment of myasthenia gravis.

Myasthenia Group and Muscle & Nerve Centre

Myasthenia Group

The Group is supported by a grant from the Myasthenia Gravis Association. It provides a centre of excellence for the management of patients with myasthenia gravis and related disorders. This includes rare inherited forms of myasthenia (congenital myasthenia). For this specific group of patients Oxford is the nationally recognised centre and is supported by the Department of Health through its National Specialist Commissioning Advisory Group (NSCAG)service.

The Group collaborates closely with the Neurosciences Group at the Institute of Molecular Medicine which undertakes internationally recognised research in the field of myasthenia and related disorders.

A clinical research fellow, funded jointly by the Myasthenia Centre and the Muscle & Nerve Centre, alternates between the two Centres.

Muscle & Nerve Group

The Group is supported by a grant from the Muscular Dystrophy Campaign. Its aim is to provide an integrated approach to the management of patients with neuromuscular disorders. The grant includes the funding of a dedicated muscle clinic physiotherapist and a specialist care advisor. The Centre is involved in several areas of clinical research (e.g. diagnosis and management of cardiomyopathy in association with muscular dystrophies) and also collaborates closely with many other research groups and laboratories around the world (e.g. identifying new genes associated with neuromuscular disorders).

A clinical research fellow, funded jointly by the Myasthenia Centre and the Muscle & Nerve Centre, alternates between the two Centres.