Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis

Multicenter, double-blind, placebo-controlled trial at three Italian centers in adults aged 18-75 years with spinal-onset, clinically probable or definite ALS by revised El Escorial criteria. Patients had disease duration <18 months at entry and were already receiving riluzole; 17 participants were randomized to TUDCA and 17 to placebo.

Tauroursodeoxycholic acid (TUDCA) dihydrate was given orally at 1 g twice daily for 54 weeks, added to background riluzole. The active product contained 250 mg tauroursodeoxycholic acid dihydrate per tablet; placebo tablets were identical in appearance.

TUDCA was well tolerated and was associated with signals of slower functional decline versus placebo. The primary responder outcome favored TUDCA: 13 (87%) versus 6 (43%) patients, P = 0.021, and baseline-adjusted ALSFRS-R at study end was higher with TUDCA (23.3 [19.9-26.6] vs 16.3 [12.9-19.7]; P = 0.007). The ALS-FRS-R slope during treatment was less steep with TUDCA (-0.262 vs -0.388; P < 0.01), and the bulbar subscore also favored TUDCA at end of study (3.8 [2.2-5.4] vs 1.9 [0.8-2.9]; P = 0.037). Study-related adverse events were reported in 2 events (13.3%) with TUDCA and 3 events (21.4%) with placebo, supporting a favorable safety profile.

This was a small pilot study with only 34 randomized patients and fewer analyzed for safety, which limits precision and generalizability. The follow-up was relatively short for ALS, and the trial was conducted in a selected early spinal-onset ALS population already treated with riluzole, so results may not extend to other ALS phenotypes or later disease stages. The survival comparison was not statistically significant (P = 0.092), so the evidence for disease-modifying benefit remains preliminary.