Three potential neuroprotective agents have proved unsuccessful in treating secondary progressive multiple sclerosis (SPMS).
A randomised controlled trial did not reveal any effect of amiloride, fluoxetine or riluzole on slowing percentage brain volume change (PBVC) when compared to placebo.
Multiple sclerosis includes both inflammatory and neurodegenerative pathological mechanisms. SPMS is the major cause of disease-associated costs, both to individuals and health care systems, and therefore is a key target for therapeutic development.
This study group had identified amiloride, fluoxetine, riluzole as potential neuroprotective agents in SPMS from a systematic literature review. The study measured volumetric MRI PBVC from baseline to 96 weeks. The study was designed to be adequately powered and enrolled a total of 445 patients.
None of the investigated agents showed any effect on slowing PBVC when compared to the placebo. No emergent safety issues were reported. The incidence of serious adverse events was low and similar across study groups.
The absence of evidence for neuroprotection in this adequately powered trial indicates that exclusively targeting these aspects of axonal pathobiology in patients with SPMS is insufficient to mitigate neuroaxonal loss.
These findings argue for investigation of different mechanistic targets and future consideration of combination treatment trials. This trial provides a template for future simultaneous testing of multiple disease-modifying medicines in neurological medicine.