A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise
Main Article Content
Abstract
Mucopolysaccharidoses III (MPS III, Sanfilippo syndrome) is a subtype of the Mucopolysaccharidoses (MPS), a group of inherited lysosomal disorders caused by a deficiency of lysosomal enzymes responsible for catabolizing glycosaminoglycans (GAGs). Although MPS III is rare, MPS diseases as a group are relatively frequent with an overall incidence of approximately 1 in 20,000 – 25,000 births. MPS III are paediatric diseases, which cause learning difficulties, behavioural disorders and dementia, as well as skeletal deformities and ultimately result in premature death. There are currently no approved treatments for MPS III, but a number of therapeutic approaches are under development. In the past 30 years, research using cellular and animal models have led to clinical trials involving enzyme replacement therapy (ERT), substrate reduction therapy (SRT) and gene therapy, while stem cells approaches remain at the pre-clinical stage. Although safety and clinical efficacy in animal models have shown promise, the results of clinical trials have proved costly and shown limited therapeutic effects. In this review, we describe the progress that has been made for ERT, SRT, gene therapy and stem cell therapies, highlighting the obstacles and work that needs to be done to bring us closer to a real treatment for these devastating diseases.
Keywords:
Mucopolysaccharidoses III, Sanfilippo syndrome, lysosomal storage disease, neurodegeneration, enzyme replacement therapy, gene therapy, substrate reduction therapy, stem cell therapy, clinical trial
Article Details
How to Cite
PEARSE, Yewande; IACOVINO, Michelina.
A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise.
Medical Research Archives, [S.l.], v. 8, n. 2, feb. 2020.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2045>. Date accessed: 05 nov. 2024.
doi: https://doi.org/10.18103/mra.v8i2.2045.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Jakobkiewicz-Banecka J, Gabig-Ciminska M, Kloska A, et al. Glycosaminoglycans and mucopolysaccharidosis type III. Frontiers in bioscience (Landmark edition). Jun 1 2016;21:1393-1409.
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6. Klein U, Kresse H, von Figura K. Sanfilippo syndrome type C: deficiency of acetyl-CoA:alpha-glucosaminide N-acetyltransferase in skin fibroblasts. Proc. Natl. Acad. Sci. U. S. A. Oct 1978;75(10):5185-5189.
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9. Cross EM, Hare DJ. Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders. J. Inherit. Metab. Dis. Mar 2013;36(2):189-200.
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13. Gaffke L, Pierzynowska K, Piotrowska E, Wegrzyn G. How close are we to therapies for Sanfilippo disease? Metab. Brain Dis. Feb 2018;33(1):1-10.
14. Lancaster MA, Knoblich JA. Generation of cerebral organoids from human pluripotent stem cells. Nat. Protoc. Oct 2014;9(10):2329-2340.
15. Allende ML, Cook EK, Larman BC, et al. Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation. J. Lipid Res. Mar 2018;59(3):550-563.
16. Camp JG, Badsha F, Florio M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl. Acad. Sci. U. S. A. Dec 22 2015;112(51):15672-15677.
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