Abstract:
BACKGROUND:TCH346 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. METHODS:Patients 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). RESULTS:Five 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). CONCLUSION:The trial revealed no evidence of a beneficial effect of TCH346 on disease progression in patients with ALS.
journal_name
Neurologyjournal_title
Neurologyauthors
Miller R,Bradley W,Cudkowicz M,Hubble J,Meininger V,Mitsumoto H,Moore D,Pohlmann H,Sauer D,Silani V,Strong M,Swash M,Vernotica E,TCH346 Study Group.doi
10.1212/01.wnl.0000269676.07319.09subject
Has Abstractpub_date
2007-08-21 00:00:00pages
776-84issue
8eissn
0028-3878issn
1526-632Xpii
69/8/776journal_volume
69pub_type
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