Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare lysosomal storage disorders caused by deficient acid ceramidase (ACDase) activity. Although both conditions are caused by mutations in the ASAH1 gene, clinical presentations differ considerably. FD patients usually die in childhood, while SMA-PME patients can live until adulthood. There is no treatment for FD or SMA-PME. Hematopoietic stem cell transplantation (HSCT) and gene therapy strategies for the treatment of ACDase deficiency are being investigated. We have previously generated and characterized mouse models of both FD and SMA-PME that recapitulate the symptoms described in patients. Here, we show that HSCT improves lifespan, behavior, hematopoietic system anomalies, and plasma cytokine levels and significantly reduces histiocytic infiltration and ceramide accumulation throughout the tissues investigated, including the CNS, in both models of ACDase-deficient mice. HSCT was also successful in preventing lesion development and significant demyelination of the spinal cord seen in SMA-PME mice. Importantly, we note that only early and generally pre-symptomatic treatment was effective, and kidney impairment was not improved in either model.

• Klíčová slova
• Farber disease, HSCT, Lysosomal storage disorders, central nervous system, ceramides, spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME),
• MeSH
• ceramidy metabolismus   MeSH
• Farberova nemoc * terapie   genetika   MeSH
• kyselá ceramidasa * genetika   metabolismus   MeSH
• lidé MeSH
• mícha metabolismus   patologie   MeSH
• modely nemocí na zvířatech MeSH
• myoklonické epilepsie progresivní genetika   terapie   metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Asah1 protein, mouse MeSH Prohlížeč
• ceramidy MeSH
• kyselá ceramidasa * MeSH