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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.

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).

Enzyme replacement therapy (ERT) has recently became available for Pompe disease. Data on the effects of ERT on physiological variables related to exercise tolerance have never been published. Pulmonary gas exchange, cardiac output (by impedance cardiography), and vastus lateralis muscle O2 extraction (by near-infrared spectroscopy) were determined during cycle ergometer exercise in a 50-yr-old patient before and after 1, 12, and 24 months of ERT. At the same constant-workload submaximal exercise, RPE, R, pulmonary ventilation, and HR were lower during ERT versus before, suggesting an increased exercise tolerance. Peak oxygen uptake (V ̇ O2peak) increased by 35% from before (0.64 L/min or 11.4 mL/kg/min) to 1 month (0.88 L/min or 15.7 mL/kg/min) of treatment and did not significantly change thereafter. Also, peak cardiac output significantly increased during ERT, whereas peak skeletal muscle fractional O2 extraction was unchanged compared with before. Improvements of peak exercise capacity and exercise tolerance at submaximal workloads were observed in a patient with Pompe disease after 1 month of ERT, with no further changes during the ensuing treatment period (up to 24 months).