Improved therapeutic approach for spinal muscular atrophy via ubiquitination-resistant survival motor neuron variant.

ABSTRACT:

Background

Zolgensma is a gene-replacement therapy that has led to a promising treatment for spinal muscular atrophy (SMA). However, clinical trials of Zolgensma have raised two major concerns: insufficient therapeutic effects and adverse events. In a recent clinical trial, 30% of patients failed to achieve motor milestones despite pre-symptomatic treatment. In addition, more than 20% of patients showed hepatotoxicity due to excessive virus dosage, even after the administration of an immunosuppressant. Here, we aimed to test whether a ubiquitination-resistant variant of survival motor neuron (SMN), SMN^K186R, has improved therapeutic effects for SMA compared with wild-type SMN (SMN^WT).

Methods

A severe SMA mouse model, SMA type 1.5 (Smn^-/-; SM

SUBMITTER: Rhee J 

PROVIDER: S-EPMC11294043 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature