title: Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.
abstract: Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid that is produced in the liver and used for treatment of chronic cholestatic liver diseases. Experimental studies suggest that TUDCA may have cytoprotective and anti-apoptotic action, with potential neuroprotective activity. A proof of principle approach was adopted to provide preliminary data regarding the efficacy and tolerability of TUDCA in a series of patients with amyotrophic lateral sclerosis (ALS).
  
  
  
  As a proof of principle, using a double-blind placebo controlled design, 34 ALS patients under treatment with riluzole who were randomized to placebo or TUDCA (1 g twice daily for 54 weeks) were evaluated after a lead-in period of 3 months. The patients were examined every 6 weeks. The primary outcome was the proportion of responders [those subjects with improvement of at least 15% in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope during the treatment period compared to the lead-in phase]. Secondary outcomes included between-treatment comparison of ALSFRS-R at study end, comparison of the linear regression slopes for ALSFFRS-R mean scores and the occurrence of adverse events.
  
  
  
  Tauroursodeoxycholic acid was well tolerated; there were no between-group differences for adverse events. The proportion of responders was higher under TUDCA (87%) than under placebo (P = 0.021; 43%). At study end baseline-adjusted ALSFRS-R was significantly higher (P = 0.007) in TUDCA than in placebo groups. Comparison of the slopes of regression analysis showed slower progression in the TUDCA than in the placebo group (P < 0.01).
  
  
  
  This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS.
authors: Neurologia I, Istituto Neurologico Carlo Besta, Milano, Italy.
authors: A E
authors: AE
authors: Elia
authors: Neurologia I, Istituto Neurologico Carlo Besta, Milano, Italy.
authors: S
authors: S
authors: Lalli
authors: Neurologia II, Seconda Università di Napoli, Napoli, Italy.
authors: M R
authors: MR
authors: Monsurrò
authors: Neurologia II, Seconda Università di Napoli, Napoli, Italy.
authors: A
authors: A
authors: Sagnelli
authors: Dipartimento di Neurologia, Centro Regionale SLA, AOUP 'P Giaccone', Università di Palermo, Palermo, Italy.
authors: A C
authors: AC
authors: Taiello
authors: Neurologia I, Istituto Neurologico Carlo Besta, Milano, Italy.
authors: B
authors: B
authors: Reggiori
authors: Dipartimento di Neurologia, Centro Regionale SLA, AOUP 'P Giaccone', Università di Palermo, Palermo, Italy.
authors: V
authors: V
authors: La Bella
authors: Neurologia II, Seconda Università di Napoli, Napoli, Italy.
authors: G
authors: G
authors: Tedeschi
authors: Neurologia I, Istituto Neurologico Carlo Besta, Milano, Italy.|NeuroCenter, Istituto Clinico Humanitas, Milano; Istituto di Neurologia, Università Cattolica del Sacro Cuore, Milano, Italy.
authors: A
authors: A
authors: Albanese
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D019782:Riluzole / Q000627:therapeutic use*; D013655:Taurochenodeoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D019782:Riluzole
keywords: amyotrophic lateral sclerosis; cholic acids; tauroursodeoxycholic acid