Comparative dose effectiveness of intravenous and intrathecal AAV9.CB7.hIDS, RGX-121, in mucopolysaccharidosis type II mice.

ABSTRACT: Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal disease caused by iduronate-2-sulfatase (IDS) deficiency, leading to accumulation of glycosaminoglycans (GAGs) and the emergence of progressive disease. Enzyme replacement therapy is the only currently approved treatment, but it leaves neurological disease unaddressed. Cerebrospinal fluid (CSF)-directed administration of AAV9.CB7.hIDS (RGX-121) is an alternative treatment strategy, but it is unknown if this approach will affect both neurologic and systemic manifestations. We compared the effectiveness of intrathecal (i.t.) and intravenous (i.v.) routes of administration (ROAs) at a range of vector doses in a mouse model of MPS II. While lower doses were completely ineffective, a total dose of 1 × 10⁹ gc re

SUBMITTER: Smith MC 

PROVIDER: S-EPMC10875268 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature