| First Author | Johnson TB | Year | 2023 |
| Journal | Front Genet | Volume | 14 |
| Pages | 1118649 | PubMed ID | 37035740 |
| Mgi Jnum | J:345680 | Mgi Id | MGI:7465505 |
| Doi | 10.3389/fgene.2023.1118649 | Citation | Johnson TB, et al. (2023) Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease. Front Genet 14:1118649 |
| abstractText | 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-in-human clinical trial (NCT03770572). |
