• R Miller, W Bradley, M Cudkowicz, J Hubble, V Meininger, H Mitsumoto, D Moore, H Pohlmann, D Sauer, V Silani, M Strong, M Swash, E Vernotica, and TCH346 Study Group.
• California Pacific Medical Center, San Francisco, CA 94115, USA. millerrx@sutterhealth.org
• Neurology. 2007 Aug 21; 69 (8): 776-84.

BackgroundTCH346 exerts antiapoptotic effects by binding to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and blocking the apoptotic pathway in which GAPDH is involved. Apoptosis is considered to be a key pathogenic mechanism in neurodegenerative diseases including ALS.MethodsPatients were randomly assigned in a double-blind fashion to receive either placebo or one of four doses of TCH346 (1.0, 2.5, 7.5, or 15 mg/day) administered orally once daily for at least 24 weeks. The primary outcome measure was the rate of change in the revised ALS functional rating scale (ALSFRS-R). The trial design included a 16-week lead-in phase to determine each patient's rate of disease progression. The between treatment comparison was adjusted for the individual pretreatment rates of progression. The study was powered to detect a 25% reduction in the rate of decline of the ALSFRS-R as compared with placebo. Secondary outcome measures included survival, pulmonary function, and manual muscle testing (MMT).ResultsFive hundred ninety-one patients were enrolled at 42 sites in Europe and North America. There were no differences in baseline variables. There were no significant differences between placebo and active treatment groups in the mean rate of decline of the ALSFRS-R or in the secondary outcome measures (survival, pulmonary function, and MMT).ConclusionThe trial revealed no evidence of a beneficial effect of TCH346 on disease progression in patients with ALS.

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