特集 神経疾患治療の進歩2024
脊髄小脳変性症の治療の進歩
キーワード:
multiple system atrophy,
α–synuclein,
spinocerebellar degeneration,
spinocerebellar ataxia,
disease–modifying therapy
2025 年 42 巻 5 号 p. 823-827
詳細
2025 年 42 巻 5 号 p. 823-827
Multiple system atrophy (MSA) and the hereditary spinocerebellar ataxias (SCAs) remain progressive, disabling disorders for which disease–modifying therapies (DMTs) have long been elusive. Over the past five years, however, development has diversified across complementary biological axes while outcome measures and natural–history resources have matured, together strengthening trial readiness.
For MSA, DMT programs cluster around five themes : (1) α–synuclein–directed approaches (passive/active immunization, antisense oligonucleotides, and oligomer modulators) with phase 2 signals but mixed primary outcomes ; a phase 3 program for the antibody amlenetug is underway. (2) Oligodendroglial support via S1P5 receptor agonism is in randomized evaluation. (3) Mitochondrial/CoQ10 pathway modulation has yielded a positive phase 2 signal for high–dose ubiquinol on UMSARS Part II. (4) Metal homeostasis targeting―exemplified by the iron–chaperone ATH434―has produced encouraging early clinical and imaging readouts. (5) Cell therapy with intrathecal mesenchymal stromal cells shows feasibility in small controlled studies. Importantly, negative trials (e.g., sirolimus ; myeloperoxidase inhibition) refine priorities and trial design.
For SCA, the pipeline is anchored by (a) gene– and sequence–directed strategies, (b) glutamate modulation (troriluzole), (c) proteostasis/autophagy modulators with mixed results, (d) metabolic interventions where primary CoQ10 deficiency is clinically actionable, and (e) exploratory cell–based approaches.
Translational enablers include earlier diagnosis and biologically grounded stratification, robust natural–history platforms, refined scales, fluid and imaging biomarkers, and digital gait/speech measures suited to decentralized trials.
In summary, DMT development for MSA and SCA is entering a multi–pathway phase. Success will likely depend on earlier–stage enrollment, genetics– and biology–based subtyping, and rigorous, patient–centered endpoints while interpreting external–control evidence with appropriate caution.
