Amyotrophic lateral sclerosis (ALS) is a chronic non-communicable neurodegenerative rare disease that affects motor neurons in the brain, brainstem and spinal cord, resulting in progressive weakness and atrophy of voluntary skeletal muscles. ALS has an estimated prevalence of 5.40 cases per 100.000 population, corresponding to 40.000 patients at European level, and causes around 11,000 deaths each year. Although much has been achieved over the last two decades in understanding the disease complexity in ALS, there is a pressing need to find disease-modifying therapies that will slow disease progression and enable patients to gain any length in survival. Although this is a formidable challenge, there is one drug (riluzole) that slightly prolongs survival in ALS and is still the only agent with a “disease-modifying” effect. The effect of riluzole on survival in ALS is modest, but indicates that modifying disease progression is a realistic goal. Nonetheless, all subsequent drugs tested in ALS have failed to deliver advances in patient care.
The “Safety and efficacy of tauroursodeoxycholic acid as add-on treatment in patients affected by amyotrophic lateral sclerosis” (TUDCA-ALS) study proposes a novel approach to overcome the current therapeutic impasse. TUDCA-ALS takes advantage of the results of a recent phase IIb study showing that, in patients who received TUDCA in addition to riluzole, the per-year decline rate in the revised-ALS functional rating scale (ALSFRS-R) was about 7 points smaller (on a 0-48 score) compared to riluzole only. This corresponds to a prolongation of median survival by 4-5 months. This strong indication of efficacy is further supported by the evidence that TUDCA has cytoprotective properties in animal models of neurodegenerative diseases.
TUDCA-ALS aims to confirm and further measure the efficacy of TUDCA as a disease-modifier in ALS in a large-scale, phase III, clinical trial. We have assembled a consortium composed of leading European centres with established experience in ALS and a strong catching capability on this patient population. We plan to enrol 440 participants across seven countries in Europe (Italy, Germany, United Kingdom, France, Belgium, Netherlands and Ireland). We have also selected solid biomarkers related to disease progression and cytoprotective activity to test during the treatment period.
