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New Therapy for LHON?
Encourging results for new gene therapy. Dermot McGrath reports from Hamburg
The first clinical trial results of a new gene therapy for Leber hereditary optic neuropathy (LHON) have shown promising safety and efficacy data with clinically meaningful and sustained visual acuity improvement without toxicity after 12 months of follow-up.
Presenting the initial results of post-intravitreal administration of NFS-02 (Wuhan Neurophth Biological Technology) as a LHON treatment, Qiutang Li PhD said the therapy was well tolerated by patients, with no serious adverse events observed thus far. Significant best-corrected visual acuity gains were observed in 6 out of 10 patients at 12 months in the treated eye.
“These initial results are very promising, as there is currently no effective treatment for LHON,” Dr Li said.
LHON is an inherited mitochondrial disorder characterised by sudden and progressive bilateral vision loss—usually in young males aged 14 to 21, due to the degeneration of retinal ganglion cells. A G3460A point mutation in the ND1 mitochondrial gene causes approximately 13% to 25% of LHON cases, Dr Li explained.
NFS-02 uses a recombinant adeno-associated virus vector (rAAV2) via intravitreal injection to deliver healthy ND1 genes to the optic ganglion cells.
“The idea is to repair the mitochondrial biological respiratory chain and restore vitality and visual function,” she said.
The study included 10 LHON patients aged between 5 and 65 years carrying the ND-1-G3460A mutation who received a single
unilateral intravitreal injection of NFS-02 at two different genome dosages. Group one received 1.5 x 108 vector genome (vg) and group two received 1.5 x 109 vg in 0.05 mL/eye.
Researchers compared the incidence of adverse events or serious adverse events—including liver and kidney function in plasma, best-corrected visual acuity (BCVA), optical coherence tomography (OCT), computerised visual field, and retinal nerve fibre layer (RNFL)—before and after treatment at 1-, 3-, 6-, and 12-month intervals.
In terms of safety, none of the patients reported drug-related serious adverse events. Treatment-emergent adverse events (TEAE) included seven cases of postoperative conjunctival hyperaemia and two cases of mildly elevated IOP.
“The conjunctival hyperaemia resolved spontaneously after one week, and the elevated IOP returned to normal after discontinuation of topical tobramycin-dexamethasone,” Dr Li said.
The BCVA showed a clinically meaningful improvement from baseline. A gain of at least -0.3 logMAR (+15 ETDRS letters) was reported in 66.7% of treated eyes in group one and 50% of treated eyes in group two. The higher dose group also showed a statistically significant improvement in visual field index and mean deviation measures at 12 months.
Summing up, Dr Li said this first clinical study of NFS-02 validates the potential of gene replacement therapy as a promising treatment for LHON, but further study is needed to confirm the results and better understand the dose-related effect of the treatment.
Dr Li presented the results at the 22nd EURETINA Congress in Hamburg, Germany. Qiutang Li PhD is Chief Scientific Officer for Neurophth Therapeutics Ltd, China. qiutang.li@neuroptht.com
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