Developing a treatment for multiple system atrophy

Abstract

Multiple system atrophy (MSA) is a neurodegenerative disease that is associated with various degrees of cerebellar ataxia or parkinsonism, pyramidal disturbances, and sleep disturbances, in addition to autonomic neuropathy. The median life expectancy from disease onset is reported to be 9 years, with a relatively poor prognosis. Symptomatic treatment of autonomic and parkinsonian symptoms may be useful in the short term, but there is a lack of disease–modifying therapies for MSA. In recent years, various therapeutic approaches for MSA are under development, including α–synuclein–targeted therapy (Epigallocatechin gallate and Rifampicin to inhibit pathological aggregation of α–synuclein, Lithium to promote α–synuclein removal, α–synuclein immunotherapy, and nucleic acid drugs to inhibit α–synuclein expression), neuroinflammation–targeted therapy (Minocycline, Fluoxetine, and Verdiperstat), neuroprotection (Rasagiline and Exenatide), and cell therapy (Mesenchymal stem cell therapy). We are developing a novel approach to slow the disease progression of MSA by high–dose ubiquinol supplementation, based on the elucidation of the genetic factors of MSA. Although many disease–modifying therapies for MSA have been developed and each has a number of genetic and cellular biological rationales, no reliable therapeutic approaches have yet been established. Clinical trials are currently underway and are expected to establish effective treatments targeting multiple mechanisms in future.