title: Intrathecal thyrotropin-releasing hormone does not alter the progressive course of ALS: experience with an intrathecal drug delivery system.
abstract: 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.
authors.affiliation: Department of Neurology, Tufts University, Boston, MA 02111.
authors.forename: T L
authors.initials: TL
authors.lastname: Munsat
authors.forename: J
authors.initials: J
authors.lastname: Taft
authors.forename: I M
authors.initials: IM
authors.lastname: Jackson
authors.forename: P L
authors.initials: PL
authors.lastname: Andres
authors.forename: D
authors.initials: D
authors.lastname: Hollander
authors.forename: L
authors.initials: L
authors.lastname: Skerry
authors.forename: M
authors.initials: M
authors.lastname: Ordman
authors.forename: D
authors.initials: D
authors.lastname: Kasdon
authors.forename: L
authors.initials: L
authors.lastname: Finison
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable; D007278:Injections, Spinal; D008297:Male; D008875:Middle Aged; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage*
chemical_list: D013973:Thyrotropin-Releasing Hormone