Preclinical Assessment of Mitochondrial-Targeted ND4 Gene Therapy for Leber Hereditary Optic Neuropathy.

ABSTRACT:

Purpose

The purpose of this study was to establish preclinical safety data to advance mitochondrial targeted AAV-delivered human ND4 (MTSAAV/hND4) for treatment of Leber Hereditary Optic Neuropathy (LHON).

Methods

MTSAAV/hND4 was bilaterally injected into mouse eyes to evaluate potential adverse effects on visual function using serial pattern electroretinograms (PERGs) and spectral-domain optical coherence tomography (SD-OCT). In rats, MTSAAV/hND4 was administered unilaterally to assess toxicity, biodistribution, and neutralizing antibody levels. Control groups include PBS-injected and untreated naïve mice and rats.

Results

No significant adverse effects on visual function were observed in mice treated with MTSAAV/hND4. Retinal thickness remained largely stable, with

SUBMITTER: Dong Y 

PROVIDER: S-EPMC12663894 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature