Am J Med Genet A. 2025 Sep 19:e64258. doi: 10.1002/ajmg.a.64258. Online ahead of print.
ABSTRACT
Acid sphingomyelinase deficiency (ASMD), or Niemann-Pick disease types A, B, and A/B, is a rare lysosomal storage disorder caused by SMPD1 mutations. Clinical forms range from severe neurovisceral (type A) to chronic visceral (type B), mainly affecting the liver, spleen, and lungs. Until 2022, treatment was limited to supportive care. The approval of olipudase alfa for the non-central nervous system (CNS) manifestations of ASMD marked a major advance, with trials showing improvements in organ volumes and lung function. This meta-analysis evaluates the broader clinical impact of olipudase alfa in ASMD. A systematic search of Cochrane, PubMed, and Embase identified RCTs and cohort studies on olipudase alfa in patients with ASMD. Primary outcomes included mean change in %DLco, %Liver volume, and %Spleen volume; other secondary outcomes were also assessed. Study selection followed PRISMA guidelines, and statistical analyses were conducted using R software. The study was registered in PROSPERO CRD420251032281. Three studies (One RCT) encompassing 46 patients were included. Follow-up duration ranged from 1 to 6.5 years. All patients received olipudase alfa; only one study included a placebo group. Pooled results showed a mean DLco increase of 34.63% (95% CI: 26.09-43.18), a liver volume reduction of -37.76% (95% CI: -49.78 to -25.75), and a spleen volume reduction of -49.46% (95% CI: -57.39 to -41.53) after 2 years. The olipudase alfa demonstrates substantial clinical benefits in ASMD, significantly improving lung function and reducing organomegaly. Further studies are needed to confirm long-term safety and efficacy.
PMID:40974024 | DOI:10.1002/ajmg.a.64258
