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Single, off-the-shelf treatment of Neuropathic Mucopolysaccharidoses with iPSC-derived microglia [scRNA-seq]

GSE224136 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2024/07/22 Platform GPL11154
Summary
Lysosomal storage disorders (LSDs) are a group of inherited metabolic disorders . A subgroup of LSDs is called Mucopolysaccharidoses (MPS), where accumulation of glycosaminoglycans causes a progressive degenerative disorder. The central nervous system (CNS) is particularly impacted with developmental delays, neurological regression, and early mortality. Current treatments are often insufficient to fully address the clinical need. Here we report the use of microglia derived from healthy human induced pluripotent stem cells (hiPSCs) as a potential one-time, allogeneic off-the-shelf cell therapy for several MPS. iPSC-derived microglia, termed MG01   , are replete with wild-type levels of lysosomal enzymes and we show that MG01 can deliver the functional enzyme into four different MPS knockout cell lines via mannose-6-phosphate receptor-mediated endocytosis in vitro. We then show that a single administration of MG01 provides sufficient enzyme to prevent behavioral deficits in two different animal models of MPS, efficacious to at least eight months after transplantation.
Published in
Ready-to-use iPSC-derived microglia progenitors for the treatment of CNS disease in mouse models of neuropathic mucopolysaccharidoses
Douvaras P, Buenaventura DF, Sun B et al. · Nature communications 2024 · PMID 39284802 · doi:10.1038/s41467-024-52400-8
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Direct links to NCBI, no account and no request form: the whole study as GSE224136_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA929959 and SRA study SRP420281. Searching any of these in the dataset finder brings you back here.

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