筋疾患の治療の進歩

抄録

Until recently, there had been no cure for many of muscle diseases. However, now several lines of clinical trials are being conducted for Duchenne muscular dystrophy (DMD) and other muscle disorders. Among them, exon skipping therapy seems a most promising strategy that targets DMD patients with deletions. Eterplirsen was approved by U.S. Food and Drug Administrations with conditions. Read–through agent, ataluren, has obtained a conditional approval from European Medicines Agency. In Japan, phase 2 clinical trial is being conducted using arbekacin based upon its read–through activity higher than that of gentamycin. An anti–myostatin monoclonal antibody, PF–06252616, which is expected to increase muscle volume, is under phase 2 clinical trial. Another hypertrophying agent, bimagrumab, a monoclonal antibody to type IIB activin receptor, did not reach the primary end point of global clinical trial against inclusion body myositis, for which no efficacious therapy has been known. GNE myopathy is caused by missense in GNE gene that encodes a protein with enzymatic activities of UDP–GlcNAc 2–epimerase and ManNAc kinase. Accordingly, sialic acid production is reduced and cells are hyposialylated. This hyposialylation status can be recovered by simply giving sialic acid. Furthermore, myopathic phenotype in the mouse is almost completely suppressed by oral administration of sialic acid. Based upon these in vitro and in vivo results, slow release tablets of sialic acid (SA–ER) is now under phase III clinical trial in North America and European countries. In diagnostic point of view, immune–mediated necrotizing myopathy and sporadic late onset nemline myopathy should be considered. Patient registry and natural history of the disease need to be established for clinical trials for rare disorders to be successful.