Abstract
Presentation Description :
Introduction: LHON was the first identified inherited human disease associated with point mutations in mitochondrial DNA (mtDNA) and it is considered the most common mitochondrial genetic disorder. The mitochondrial genotype is the most significant prognostic factor of visual outcome, followed by age at onset of vision loss.
The gene therapy approach is based on the allotopic expression of the therapeutic ND4 Transgene, refined in terms of efficiency in mitochondrial import<span style="font-size:10.8333px">.</span>
Clinical trials of ocular gene therapy for the treatment of ND4-LHON
SPONSOR : Huazhong University of Science and Technology, China
Gene Therapy Product : AAV2-ND4 with mitochondrial targeting sequence
Study population : ND4 LHON patients Phase 1/2 - Open-label n=9 and Phase 2/3 – Open-label n= 149
ClinicalTrials.gov NCT01267422 and NCT03153293
SPONSOR : Bascom Palmer Eye Institute, University of Miami, USA
Gene Therapy Product : scAAV2-P1ND4v2
Study population : ND4 LHON patients Phase1/2 - Open-label N=14
ClinicalTrials.gov. NCT02161380
SPONSOR : GenSight Biologics, France
Gene Therapy Product : rAAV2/2-ND4 with mitochondrial targeting sequence
Study population : ND4 LHON patients : Phase 1/2 - Open-label N=15 and Four Phase 3 studies: double-masked, randomised, sham or placebo-controlled N=174
Clinical Trial Registration information : REVEAL: ClinicalTrials.gov NCT02064569 /REVERSE: NCT02652780 /RESCUE: NCT02652767 /RESTORE: NCT03406104 /REFLECT: NCT03293524
All these studies have confirmed that ocular gene therapy for LHON via IVT injection has an overall good safety profile with excellent systemic tolerability and mostly mild ocular side effects, responsive to conventional ophthalmologic treatments.
All 3 research groups assessing the efficacy and safety of unilateral IVT gene therapy in ND4-LHON patients reported an unexpected, sustained, and clinically meaningful improvement of BCVA in the untreated contralateral eyes not consistent with the reported natural history of the disease.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.