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- Title
Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease.
- Authors
Johnson, Tyler B.; Brudvig, Jon J.; Likhite, Shibi; Pratt, Melissa A.; White, Katherine A.; Cain, Jacob T.; Booth, Clarissa D.; Timm, Derek J.; Davis, Samantha S.; Meyerink, Brandon; Pineda, Ricardo; Dennys-Rivers, Cassandra; Kaspar, Brian K.; Meyer, Kathrin; Weimer, Jill M.
- Abstract
CLN3 disease, caused by biallelic mutations in the CLN3 gene, is a rare pediatric neurodegenerative disease that has no cure or disease modifying treatment. The development of effective treatments has been hindered by a lack of etiological knowledge, but gene replacement has emerged as a promising therapeutic platform for such disorders. Here, we utilize a mouse model of CLN3 disease to test the safety and efficacy of a cerebrospinal fluid-delivered AAV9 gene therapy with a study design optimized for translatability. In this model, postnatal day one administration of the gene therapy virus resulted in robust expression of human CLN3 throughout the CNS over the 24-month duration of the study. A range of histopathological and behavioral parameters were assayed, with the therapy consistently and persistently rescuing a number of hallmarks of disease while being safe and well-tolerated. Together, the results show great promise for translation of the therapy into the clinic, prompting the launch of a first-inhuman clinical trial (NCT03770572).
- Subjects
GENE therapy; GENE expression; NEURODEGENERATION; THERAPEUTICS; NEURONAL ceroid-lipofuscinosis
- Publication
Frontiers in Genetics, 2023, Vol 14, p01
- ISSN
1664-8021
- Publication type
Article
- DOI
10.3389/fgene.2023.1118649