A CINRG PILOT TRIAL OF OXATOMIDE IN STEROID-NAÏVE DUCHENNE MUSCULAR DYSTROPHY

Objectives: Duchenne muscular dystrophy (DMD) is the most common and devastating type of muscular dystrophy. Mast cells have been implicated in the pathophysiology of DMD and its animal models. The mast cell stabilizer oxatomide has shown promise in a pre-clinical screening platform that uses the homologous mdx mouse model of DMD. With CINRG (Cooperative International Neuromuscular Research Group), we have tested the hypothesis that oxatomide specifically targets the pathophysiological cascade of DMD by blocking the mast cell mediator cascade and inhibiting dendritic cell's release of cytokines.

Methods: We tested the efficacy and safety of oxatomide in 14 ambulant steroid-naive DMD boys aged 5–10 years, in a pilot open-label two-center clinical trial with a 3 months medication-free leadin period followed by a 6 months treatment period with oral oxatomide (30mg/day). Drug efficacy was tested by measuring muscle strength quantitatively (QMT, 10 muscle groups) and manually (MMT, 34 muscle groups), and by timed functional tests.

Results: Repetitive measure analysis was applied using linear mixed-effects models, comparing intercepts and slopes of lead-in and treatment periods. Within the limitations of a smaller non-controlled trial, we conclude that 6 months oxatomide treatment does not improve muscle strength or function in a group of 5 to 10 year old DMD patients. There were no serious adverse events and overall oxatomide was well tolerated.