ArticleAnnals of clinical and translational neurology2026
Re-Purposing Sapropterin (Kuvan) for ACTA2-Related Multisystemic Smooth Muscle Dysfunction Syndrome: A Translational Mechanistic and First-In-Human Therapeutic Report.
Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Re-Purposing Sapropterin (Kuvan) for ACTA2-Related Multisystemic Smooth Muscle Dysfunction Syndrome: A Translational Mechanistic and First-In-Human Therapeutic Report.Annals of clinical and translational neurology · 2026Article
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10 authors.
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Abstract
Multisystemic smooth muscle dysfunction syndrome (MSMDS) is an ultra-rare, ACTA2-related disorder characterized by severe cerebrovascular disease, aortic aneurysms, and smooth muscle dysfunction. Using molecular dynamics simulations and in silico drug screening, we identified that sapropterin dihydrochloride (Kuvan) is a candidate capable of restoring p.R179H mutation disrupted actin polymerization. Patient-derived fibroblasts demonstrated improved actin organization with Kuvan treatment. Off-label treatment in a single pediatric patient with ACTA2-MSMDS resulted in observed cerebrovascular stabilization and clinical improvement on longitudinal follow-up. These findings provide first-in-human n-of-1 translational evidence supporting sapropterin as a potential disease-modifying therapy for ACTA2-related vasculopathies, while gene-directed therapies are awaited. Further studies are needed to establish a robust therapeutic effect and to elucidate the mechanisms underlying the observed cerebrovascular benefit.
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