Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.
BACKGROUND AND PURPOSE
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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS.
['Elia|A E|AE|', 'Lalli|S|S|', 'Monsurrò|M R|MR|', 'Sagnelli|A|A|', 'Taiello|A C|AC|', 'Reggiori|B|B|', 'La Bella|V|V|', 'Tedeschi|G|G|', 'Albanese|A|A|']
D000328:Adult D000368:Aged D000690:Amyotrophic Lateral Sclerosis D004311:Double-Blind Method D004359:Drug Therapy, Combination D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D018696:Neuroprotective Agents D017063:Outcome Assessment, Health Care D010865:Pilot Projects D019782:Riluzole D013655:Taurochenodeoxycholic Acid
tauroursodeoxycholic acid amyotrophic lateral sclerosis cholic acids