A combination of sodium phenylbutyrate and taurursodiol has shown tantalising preliminary results against functional decline in patients with amyotrophic lateral sclerosis (ALS).
In a 24-week phase 2 randomised controlled trial, US researchers showed that the combination – also known as tauroursodeoxycholic acid – was associated with a 25% drug-associated slowing of the rate of functional decline in patients with more rapidly progressive forms of ALS.
Results from the multicentre study, published in NEJM, showed a difference of 0.42 points per month in rate of change in the total score on the ALS Functional Rating Scale–Revised (ALSFRS-R) between the active-drug group (89 participants) and placebo (48 participants).
The mean rate of change in the ALSFRS-R score was −1.24 points per month with the active drug and −1.66 points per month with placebo (P=0.03). The study authors noted that most prominent changes were seen with the fine-motor subscale of ALSFRS-R scores and less apparent for the other subscales.
However there were no significant differences between the groups in secondary outcomes such as rate of decline in isometric muscle strength or breathing function, change in levels of pNF-H levels (a biomarker of motor neuron degeneration), and the time to events including death, tracheostomy, permanent ventilation, and hospitalization.
Adverse events were more frequent with the active drug and were mainly gastrointestinal, (diarrhoea, nausea, salivary hypersecretion, and abdominal discomfort), and about 19% of patient discontinued treatment due to side effects.