Evidence that thyrotropin-releasing hormone (TRH) has prominent trophic effects 
on the motor system led to several negative therapeutic trials in amyotrophic 
lateral sclerosis, a disease of the motor system. Since TRH crosses the 
blood-brain barrier poorly, if at all, we postulated that the negative 
parenteral clinical trials could be a result of insufficient drug-receptor 
interaction. We thus carried out a blinded, placebo-controlled, crossover study 
of intrathecal TRH in 36 patients by delivery through an implanted, constant 
infusion pump achieving a steady-state CSF level comparable with that shown to 
be effective in tissue culture experiments. Utilizing a quantitative measurement 
technique to assess motor unit loss, we did not observe any alteration of the 
progressive course during 6 months on TRH and 6 months on saline placebo. 
However, the implanted pump delivery system proved to be safe, reliable, and 
well tolerated.