A Systematic Review on Disease-Modifying Therapies in Parkinsonian Disorders.
Level 1 - systematic review of randomized trials
Systematic review of clinical trials.
PubMed 42104724 · doi:10.1002/cpt.70315
What was done
A systematic review was conducted based on a literature search through May 2025 to evaluate clinical trials investigating pharmacological interventions aimed at slowing disease progression across Parkinsonian disorders (Parkinson's disease, Lewy body dementia, multiple system atrophy, and progressive supranuclear palsy).
What was found
The abstract reports no numerical data, pooled effect sizes, or study counts. Qualitatively, it reports that: - Alpha-synuclein-targeting agents (monoclonal antibodies and small molecules) demonstrated target engagement but limited clinical efficacy. - Glucocerebrosidase-enhancing agents (notably ambroxol) showed promising biomarker and clinical signals in early-phase trials. - GLP-1 receptor agonists and kinase inhibitors showed mixed results, with some reaching phase 3. - Neurotrophic factors, neuroprotective therapies, stem cells, and anti-inflammatory agents showed limited evidence of efficacy. - Repurposed drugs (memantine, riluzole) showed preliminary benefits without confirmatory trials. - No disease-modifying therapy has been approved for any Parkinsonian disorder.
Why it matters
This review highlights that broad, non-stratified clinical trial designs have repeatedly failed to establish disease modification in Parkinsonian disorders, pointing to the critical need for biomarker-driven patient selection and mechanistic trial endpoints.
Limits
The abstract provides no sample sizes, specific trial counts, or quantitative effect metrics. The vast majority of evaluated research is restricted to Parkinson's disease, with sparse data for atypical Parkinsonian disorders. Reliance on conventional clinical rating scales (like UPDRS) and clinical heterogeneity remain substantial confounding limitations across the underlying trials.
Cited by
- supports No medications currently used to treat Parkinson's disease have been demonstrated to slow disease progression.