An update on multiple system atrophy

Purpose of reviewMultiple system atrophy (MSA) is a rapidly progressive synucleinopathy characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Here, we provide an update on alpha-synuclein's role in MSA pathophysiology and review the new Movement Disorders Society (MDS) diagnostic criteria and the utility of alpha-synuclein-based biomarkers. We also highlight ongoing efforts toward clinical trial readiness and review potential disease-modifying therapies undergoing clinical trials.Recent findingsA role of urinary tract infections in triggering alpha-synuclein aggregation and contribution of genes implicated in oligodendroglial development have been suggested in the MSA pathophysiology. The clinically probable MSA category of the new diagnostic criteria shows improved accuracy in early disease stages. Predictors of phenoconversion from pure autonomic failure to MSA are now better defined. Alpha-synuclein strains in CSF and serum, phosphorylated alpha-synuclein deposits in the skin, and brain alpha-synuclein pathology visualized using PET ligand [18F]ACI-12589 are emerging as valuable diagnostic tools. Clinical trials in MSA investigate drugs targeting alpha-synuclein aggregation or preventing alpha-synuclein expression, along with stem cell and gene therapies to halt disease progression.SummaryNew MSA diagnostic criteria and alpha-synuclein-based biomarkers may enhance diagnostic accuracy while promising therapies are in development to address disease progression.