Botulinum Toxin Treatment in Hereditary Spastic Paraplegia-A Comprehensive Review and Update

Area of Science:

• Neurology
• Pharmacology
• Genetics

Background:

• Hereditary spastic paraplegia (HSP) is a group of inherited neurological disorders characterized by progressive stiffness and spasticity in the lower limbs.
• Botulinum neurotoxins (BoNTs) are increasingly explored for managing spasticity in various neurological conditions.

Purpose of the Study:

• To conduct a comprehensive literature review of clinical studies on botulinum neurotoxin therapy for hereditary spastic paraplegia (HSP).
• To critically evaluate the efficacy and safety of BoNTs in treating HSP based on available clinical evidence.

Main Methods:

• Systematic search of Medline and Scopus databases for clinical studies on BoNT therapy in HSP, published up to September 1, 2025.
• Inclusion criteria focused on English-language articles detailing study type, toxin type/dose, and treatment outcomes, excluding case reports and reviews.
• Analysis of 10 identified studies (9 adult, 1 pediatric), assessing outcomes from open-label and one double-blind, placebo-controlled trial.

Main Results:

• Open-label studies using FDA-approved botulinumtoxin-A (Botox, Dysport, Xeomin) demonstrated motor and non-motor improvements in HSP patients.
• A single double-blind study using Prosigne showed no functional improvement, highlighting a discrepancy with open-label findings.
• No studies investigated the effect of BoNTs on bladder dysfunction in HSP patients.

Conclusions:

• Current evidence from open-label studies suggests potential benefits of FDA-approved botulinumtoxin-A for HSP symptom management.
• The limited number of high-quality, double-blind, placebo-controlled trials necessitates further investigation.
• Future research should focus on rigorous studies in both children and adults, exploring early intervention and effects on various HSP-related symptoms, including bladder dysfunction.