Abstract
Mucopolysaccharidoses (MPSs) are childhood diseases caused by inherited deficiencies in glycosaminoglycans degradation. Most MPSs involve neurodegeneration, which to date is untreatable. Currently, most therapeutic strategies aim at correcting the primary genetic defect. Among these strategies, gene therapy has shown a great potential though its clinical application is challenging. We have shown previously in an MPS-IIIA mouse model that the molecular tweezer (MT) CLR01, a potent, broad-spectrum anti-amyloid small molecule, inhibits secondary amyloid storage, facilitates amyloid clearance, and protects against neurodegeneration. Here we demonstrate that combining CLR01 with AAV-mediated gene therapy, targeting both the primary and secondary pathologic storage in MPS-IIIA mice, results in a synergistic effect improving multiple therapeutic outcomes compared to each monotherapy. Moreover, we demonstrate that CLR01 is effective therapeutically in mouse models of other forms of neuronopathic MPS, MPS-I and MPS-IIIC. These strongly support developing MTs as an effective treatment option for neuronopathic MPSs, both on their own and in combination with gene therapy, to improve therapeutic efficacy and translation into clinical application.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.