Dalfampridine as a promising agent in the management of hereditary spastic paraplegia: A triple-blinded, randomized, placebo-controlled pilot trial.

Limited but encouraging results support the use of dalfampridine in patients with hereditary spastic paraplegia (HSP). Our aim was to investigate the effects of dalfampridine on walking speed, muscle length, spasticity, functional strength, and functional mobility in patients with HSP. In this triple-blinded, randomized, placebo-controlled pilot trial, four patients with HSP received dalfampridine (10 mg twice daily) in addition to physiotherapy (twice a week), and four patients received placebo in addition to physiotherapy for eight weeks. The group allocation was masked from the assessor, treating physiotherapists, and patients. The primary outcome was the Timed 25-foot Walk Test (T25FWT) at the end of the eight-week treatment. The secondary outcome measures were functional mobility, functional muscle strength, muscle length, and spasticity. The improvement in the T25FWT values was significantly higher in the experimental group than in the control group (p < 0.05). All patients in the experimental group exceeded the proposed minimally important clinical difference for T25FWT. The degrees of improvement in most muscle length and spasticity assessments and functional muscle strength were also higher in the experimental group (p < 0.05). No significant difference was observed between the groups regarding functional mobility (p > 0.05). No adverse events or side effects were noted. This pilot trial yields encouraging evidence that the combination of dalfampridine and physiotherapy may enhance muscle parameters and improve walking speed in patients with HSP. However, further research involving larger sample sizes and more comprehensive assessments is needed to validate these results and establish the clinical benefits of this treatment approach. Trial registration ID: NCT05613114 (https://clinicaltrials.gov/), retrospectively registered on November 14, 2022.