The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as
Johannes Levin1,2, Sylvia Maaß3,4, Madeleine Schuberth5
1Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität, Munich, Germany. jlevin@med.uni-muenchen.de.
Abstract:
Formation of toxic α-synuclein oligomers appears to be a key underlying pathological mechanism of synucleinopathies such as Parkinson's disease or multiple system atrophy (MSA). Given that Epigallocatechin-gallate has been shown to inhibit α-synuclein aggregation, it might represent a causal treatment option. Therefore, we set out to evaluate the safety, tolerability and a potential disease-modifying effect of Epigallocatechin-gallate in patients with MSA after 48 weeks of treatment. Power calculation was performed on existing natural history data on the progression of the Unified MSA Rating Scale as primary readout parameter. To assess the efficacy of Epigallocatechin-gallate versus placebo regarding the reduction of disease progression measured during the study period (80 % power, 5 % p level, 50 % effect size) 36 patients per group are needed. Considering a drop-out rate of 20 % a total of 86 patients will be recruited in this multicentre study. These data provide a solid rationale to investigate whether supplementation of Epigallocatechin-gallate can delay the progression of the MSA-related disability.
Insights
Epigallocatechin-gallate may slow the progression of multiple system atrophy (MSA) by inhibiting toxic alpha-synuclein aggregation. This study investigates its safety and potential disease-modifying effects in MSA patients over 48 weeks.
Area of Science:
- Neurodegenerative diseases
- Molecular mechanisms of neurodegeneration
- Pharmacological interventions
Background:
- Toxic alpha-synuclein oligomer formation is central to synucleinopathies like Parkinson's disease and multiple system atrophy (MSA).
- Epigallocatechin-gallate (EGCG) has demonstrated potential in inhibiting alpha-synuclein aggregation, suggesting a therapeutic avenue.
Purpose of the Study:
- To evaluate the safety and tolerability of Epigallocatechin-gallate in patients diagnosed with MSA.
- To assess the potential disease-modifying effects of Epigallocatechin-gallate over a 48-week treatment period.
Main Methods:
- A multicentre study involving 86 patients with MSA, accounting for a 20% drop-out rate.
- Statistical power calculations based on natural history data of the Unified MSA Rating Scale progression.
- Comparison of Epigallocatechin-gallate treatment against a placebo to measure disease progression reduction.
Main Results:
- The study is designed to detect a 50% effect size with 80% power and a 5% significance level.
- Sample size determination indicates 36 patients per group are required for efficacy assessment.
- The methodology provides a robust framework for analyzing EGCG's impact on MSA progression.
Conclusions:
- The study provides a strong rationale for investigating Epigallocatechin-gallate as a potential treatment to delay disability progression in MSA.
- Further research is warranted to confirm the therapeutic benefits of EGCG in managing synucleinopathies.
- This investigation aims to establish EGCG as a causal treatment option for MSA patients.
