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SPHINGOMYELIN SPECIES AS THERAPEUTIC TARGETS AND BIOMARKERS FOR BRAIN PATHOLOGY IN THE ACID SPHINGOMYELINASE DEFICIENCY
Angel Gaudiosoand 5 co-authors
Centro de Biologia Molecular Severo Ochoa
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS07-10AM-179
Presentation
Date TBA
Board: PS07-10AM-179
Event Information
Poster Board
PS07-10AM-179
Poster
View posterAbstract
Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder caused by mutations in the gene encoding acid sphingomyelinase, an enzyme that metabolises sphingomyelin (SM). As a consequence, SM accumulates in lysosomes and plasma membrane of cells. In the neurovisceral forms of the disease, where the mutations reduce significantly ASM activity, SM not only accumulates in cells of peripheral tissues, but also in brain cells leading to chronic neuroinflammation and neurodegeneration.
Currently, there is no treatment for the brain disease associated with ASMD, so our research focuses on finding new therapeutic approaches and selective biomarkers. By screening a repurposing compound-library in ASMko nematodes and ASMD human fibroblasts, we have identified hematoporphyrin (HP) as an SM-reducing compound. Using mice lacking ASM (ASMko), which mimic neurovisceral ASMD, we have shown the ability of HP to ameliorate disease phenotypes in primary cultured neurons and in the brain of the ASMko mice when intraperitoneally injected. Furthermore, we have identified a SM species containing a very-long-chain and heavily unsaturated fatty acid as a potential biomarker in blood specific for brain pathology in ASMD.
Altogether, these results open perspectives to improve the diagnosis and treatment of this fatal disease.
Currently, there is no treatment for the brain disease associated with ASMD, so our research focuses on finding new therapeutic approaches and selective biomarkers. By screening a repurposing compound-library in ASMko nematodes and ASMD human fibroblasts, we have identified hematoporphyrin (HP) as an SM-reducing compound. Using mice lacking ASM (ASMko), which mimic neurovisceral ASMD, we have shown the ability of HP to ameliorate disease phenotypes in primary cultured neurons and in the brain of the ASMko mice when intraperitoneally injected. Furthermore, we have identified a SM species containing a very-long-chain and heavily unsaturated fatty acid as a potential biomarker in blood specific for brain pathology in ASMD.
Altogether, these results open perspectives to improve the diagnosis and treatment of this fatal disease.
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