ArticleEMBO molecular medicine2020
Haematopoietic stem cell gene therapy with IL-1Ra rescues cognitive loss in mucopolysaccharidosis IIIA.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Anakinra in Sanfilippo syndrome: a phase 1/2 trial.Nature medicine · 2024Trial
- Short-Term Oral Spermidine Supplementation Modifies Aspects of Neurodegenerative Disease in Flies and Mice With MPS III.Journal of inherited metabolic disease · 2026Article
- Delivery of cytokines via encapsulated human astrocytes for neural immunomodulation.Biomaterials · 2026Article
- Neuroinflammation as a Novel Therapeutic Frontier for Sanfilippo Syndrome.Children (Basel, Switzerland) · 2025Review
- Single-cell RNA sequencing reveals important role of monocytes and macrophages during mucopolysaccharidosis treatment.Scientific reports · 2025Article
- Human iPSC-derived neural stem cells engraft and improve pathophysiology of MPS I mice.Molecular therapy. Methods & clinical development · 2024Article
- IL-1 receptor antagonist: etiological and drug delivery systems overview.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Anti-amyloid treatment is broadly effective in neuronopathic mucopolysaccharidoses and synergizes with gene therapy in MPS-IIIA.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Extracellular vesicles from microglial cells activated by abnormal heparan sulfate oligosaccharides from Sanfilippo patients impair neuronal dendritic arborization.Molecular medicine (Cambridge, Mass.) · 2024Article
- The Role of the Gut Microbiota in Sanfilippo Syndrome's Physiopathology: An Approach in Two Affected Siblings.International journal of molecular sciences · 2024Article
- Plasma and CSF biomarkers of aging and cognitive decline in Caribbean vervets.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Hematopoietic stem cell gene therapy to halt neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Systemic immune challenge exacerbates neurodegeneration in a model of neurological lysosomal disease.EMBO molecular medicine · 2024Article
- Article
- Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.International journal of molecular sciences · 2024Review
- Sustained long-term disease correction in a murine model of MPSII following stem cell gene therapy.Molecular therapy. Methods & clinical development · 2023Article
- An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis.Pharmaceutics · 2023Article
- Serum interleukin-1 is a new biomarker to predict the risk of rebleeding of ruptured intracranial aneurysm after admission.Neurosurgical review · 2023Article
- Upregulation of non-canonical and canonical inflammasome genes associates with pathological features in Krabbe disease and related disorders.Human molecular genetics · 2023Article
- Interleukin-1 receptor antagonist: a promising cytokine against human squamous cell carcinomas.Heliyon · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Mucopolysaccharidosis IIIA is a neuronopathic lysosomal storage disease, characterised by heparan sulphate and other substrates accumulating in the brain. Patients develop behavioural disturbances and cognitive decline, a possible consequence of neuroinflammation and abnormal substrate accumulation. Interleukin (IL)-1β and interleukin-1 receptor antagonist (IL-1Ra) expression were significantly increased in both murine models and human MPSIII patients. We identified pathogenic mechanisms of inflammasome activation, including that disease-specific 2-O-sulphated heparan sulphate was essential for priming an IL-1β response via the Toll-like receptor 4 complex. However, mucopolysaccharidosis IIIA primary and secondary storage substrates, such as amyloid beta, were both required to activate the NLRP3 inflammasome and initiate IL-1β secretion. IL-1 blockade in mucopolysaccharidosis IIIA mice using IL-1 receptor type 1 knockout or haematopoietic stem cell gene therapy over-expressing IL-1Ra reduced gliosis and completely prevented behavioural phenotypes. In conclusion, we demonstrate that IL-1 drives neuroinflammation, behavioural abnormality and cognitive decline in mucopolysaccharidosis IIIA, highlighting haematopoietic stem cell gene therapy treatment with IL-1Ra as a potential neuronopathic lysosomal disease treatment.
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Registered trials
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