The lack of effective therapy for many of the chronic neuromuscular diseases 
such as amyotrophic lateral sclerosis, hereditary motor sensory neuropathy 
(Charcot-Marie-Tooth disease), spinocerebellar degenerations and idiopathic 
polyneuropathy has led to a search for substances that may stimulate peripheral 
nerve regeneration. Two such agents that have been proposed are gangliosides 
(mixed purified bovine brain gangliosides, Cronassial) and thyrotropin releasing 
factor (TRH). Studies on both of these agents were initially reported with 
enthusiasm to be successful, but later double-blind controlled studies have 
failed to confirm these findings. This review provides critical analysis of the 
designs of studies of potentially effective agents in chronic neuromuscular 
diseases, and emphasizes the power of the placebo response, and the importance 
of designing placebos which are indistinguishable from the trial medication 
other than in the active effect.