Gene Therapy Is Expected to Treat LHON Efficiently

If a gene mutates and causes a certain genetic disease, then replace or supplement it with a new and correct copy. In theory, such a strategy can cure countless human genetic diseases. In the past, this seemed to only be seen in science fiction works, but the rapid development of life sciences is making it a reality step by step.

On December 9, 2020, an international team composed of Dr. Patrick Yu-Wai-Man from the University of Cambridge and Dr. Jose-Alain Sahel from the University of Pittsburgh published a paper titled Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy in Science Translational Medicine.

This study found that injecting an adeno-associated virus (AAV) gene therapy vector into one eye of patients with Leber's hereditary optic neuropathy (LHON) can significantly improve the vision in both eyes. In a landmark Phase III clinical trial, the research team successfully improved the vision of 78% of LHON patients through this treatment.

LHON is a degenerative disease of the optic nerve. It is caused by mutations in mitochondrial gene, which affect a special type of retinal cells-retinal ganglion cells, and in turn lead to optic nerve degeneration and rapid deterioration of binocular vision. Within a few weeks of onset, the vision of most patients will deteriorate to the level of blindness. Globally, the incidence of LHON is about one in 30,000, and most of them are men. The symptoms usually appear between the ages of 20 and 30. Site mutations in mitochondrial DNA are considered to be specific to LHON. Among the mutations, most patients carry the m.11778G>A mutation in the MT-ND4 gene.

Regrettably, although LHON is a genetic disease that can cause serious consequences, the current treatment for this blinding optic neuropathy is still very limited. Now, the latest research has brought new hope to LHON patients.

In this study, the researchers injected a viral vector containing the correct cDNA, rAAV2/2-ND4, into the vitreous cavity at the back of one eye of 37 LHON patients who were blind for 6-12 months. At the same time, the patient's other eye only received a injection. In anticipation, the research team expected that the vision of the gene-treated eye would improve, but unexpectedly, in the following two years of follow-up, 78% of the LHON patients who participated in the trial had vision improved.

On the, the best corrected visual acuity (BCVA) of the treated eyes improved by an average of 15 letters, representing, while the eyes treated with sham surgery improved by an average of 13 letters. Not only that, because some patients are still in the dynamic stage of the disease process when receiving treatment, their vision is actually better restored—the treated eyes reached 28.5 letters, and another reached 24.5 letters.

In order to investigate how monocular treatment improves the other eye, researchers conducted a study on cynomolgus monkeys and found that the improvement in vision in untreated eyes is caused by the interocular dispersion of rAAV2/2-ND4.

In recent years, gene editing technology represented by CRISPR-Cas9 has brought revolutionary changes to life science and medicine development. People have high hopes for new technologies such as gene editing and gene therapy in clinical treatment and overcoming chronic diseases. With the continuous development of gene editing technology, more and more clinical experiment results have also confirmed that gene editing and treatment have great prospects and are important development directions in the field of biomedicine in the future.

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