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Hematopoietic stem cell transplantation leads to biochemical and functional correction in two mouse models of acid ceramidase deficiency

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10488248" target="_blank" >RIV/00216208:11110/24:10488248 - isvavai.cz</a>

  • Alternative codes found

    RIV/00064165:_____/24:10488248

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=82Q7-QdqQH" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=82Q7-QdqQH</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.ymthe.2024.08.004" target="_blank" >10.1016/j.ymthe.2024.08.004</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Hematopoietic stem cell transplantation leads to biochemical and functional correction in two mouse models of acid ceramidase deficiency

  • Original language description

    Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare lysosomal storage disorders caused by deficient fi cient 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 SMAPME. Hematopoietic stem cell transplantation (HSCT) and gene therapy strategies for the treatment of ACDase deficiency fi ciency 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 fi cantly reduces histiocytic infiltration fi ltration and ceramide accumulation throughout the tissues investigated, including the CNS, in both models of ACDase-deficient fi cient mice. HSCT was also successful in preventing lesion development and significant fi cant 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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30101 - Human genetics

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Molecular Therapy

  • ISSN

    1525-0016

  • e-ISSN

    1525-0024

  • Volume of the periodical

    32

  • Issue of the periodical within the volume

    10

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    20

  • Pages from-to

    3402-3421

  • UT code for WoS article

    001331075000001

  • EID of the result in the Scopus database

    2-s2.0-85205740497