ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Fluoxetine ameliorates mucopolysaccharidosis type IIIA.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Psychiatric manifestations in Neuronal ceroid lipofuscinoses.Orphanet journal of rare diseases · 2026Pooled it
- Regulation of autophagy, lipid metabolism, and neurodegenerative pathology by heparan sulfate proteoglycans.Frontiers in genetics · 2022Pooled it
- Unveiling Mucopolysaccharidosis IIIC in Brazil: Diagnostic Journey and Clinical Features of Brazilian Patients Identified Through the MPS Brazil Network.Diseases (Basel, Switzerland) · 2025Article
- Cofactor-independent photo-enzymatic reductions with water mediated by reductive graphene quantum dots.Nature communications · 2025Article
- D1 dopamine receptor antagonists as a new therapeutic strategy to treat autistic-like behaviours in lysosomal storage disorders.Molecular psychiatry · 2025Article
- Behavioural disorders and sleep problems in Sanfilippo syndrome: overlaps with some other conditions and importance indications.European child & adolescent psychiatry · 2025Review
- A Drosophila model of mucopolysaccharidosis IIIB.Genetics · 2025Article
- Cathepsin B inhibition blocks amyloidogenesis in the mouse models of neurological lysosomal diseases MPS IIIC and sialidosis.Molecular therapy. Methods & clinical development · 2025Article
- 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
- Initiation of fluoxetine in a pediatric patient with Mucopolysaccharidosis IIIA: Early observations.Molecular genetics and metabolism reports · 2024Article
- Mucopolysaccharidosis type II zebrafish model exhibits early impaired proteasomal-mediated degradation of the axon guidance receptor Dcc.Cell death & disease · 2024Article
- Review
- The post-translational regulation of transcription factor EB (TFEB) in health and disease.EMBO reports · 2023Review
- Neurocognitive testing in a murine model of mucopolysaccharidosis type IIIA.Molecular genetics and metabolism reports · 2023Article
- TRPML1 and TFEB, an Intimate Affair.Handbook of experimental pharmacology · 2023Article
- Mucopolysaccharidoses: Cellular Consequences of Glycosaminoglycans Accumulation and Potential Targets.International journal of molecular sciences · 2022Review
- The Regulation of MiTF/TFE Transcription Factors Across Model Organisms: from Brain Physiology to Implication for Neurodegeneration.Molecular neurobiology · 2022Review
- Thalamo-hippocampal pathway regulates incidental memory capacity in mice.Nature communications · 2022Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucopolysaccharidosis type IIIA (MPS-IIIA) is an autosomal recessive disorder caused by mutations in SGSH involved in the degradation of heparan sulfate. MPS-IIIA presents severe neurological symptoms such as progressive developmental delay and cognitive decline, for which there is currently no treatment. Brain targeting represents the main challenge for therapeutics to treat MPS-IIIA, and the development of small-molecule-based treatments able to reach the CNS could be a relevant advance for therapy. Using cell-based high content imaging to survey clinically approved drugs in MPS-IIIA cells, we identified fluoxetine, a selective serotonin reuptake inhibitor. Fluoxetine increases lysosomal and autophagic functions via TFEB activation through a RagC-dependent mechanism. Mechanistically, fluoxetine increases lysosomal exocytosis in mouse embryonic fibroblasts from MPS-IIIA mice, suggesting that this process may be responsible for heparan sulfate clearance. In vivo, fluoxetine ameliorates somatic and brain pathology in a mouse model of MPS-IIIA by decreasing the accumulation of glycosaminoglycans and aggregated autophagic substrates, reducing inflammation, and slowing down cognitive deterioration. We repurposed fluoxetine for potential therapeutics to treat human MPS-IIIA disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.