Patients with hereditary forms of childhood blindness gained more than a year of vision after receiving a single experimental RNA treatment.
The gene editing research was conducted at the Perelman School of Medicine at the University of Pennsylvania.The results of the case were published on April 1 Natural medicine, Indicating that the treatment resulted in a significant change in the fovea (the most important part of the human central vision)
In international clinical trials, participants received intraocular injections of antisense oligonucleotides called sepofarsen. This short RNA molecule can work by increasing the level of normal CEP290 protein in the photoreceptor cells of the eye and improving retinal function during daytime visual conditions.
This therapy is designed for patients diagnosed with Leber Congenital Black Eye (LCA), an eye disease that mainly affects the retina, who has a CEP290 mutation, which is one of the most common genes in patients with this disease One. Patients with this form of LCA suffer from severe visual impairment, usually beginning in infancy.
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“Our results set a new standard for possible biological improvements,” said co-author Dr. Artur Cideciyan, professor of ophthalmology research at the Scheie Eye Institute at the University of Pennsylvania. “Importantly, we have established a comparator for the current ongoing gene editing therapies for the same disease, so that the relative advantages of two different interventions can be compared.”
In a 2019 study published in Nature Medicine, Cideciyan and his collaborators, including Dr. Samuel G. Jacobson, found that repeated injections of sepofarsen every three months can give 10 patients continuous vision.
The eleventh patient who detailed the treatment in the latest paper received only one injection and was examined for 15 months. Before treatment, the patient’s visual acuity was reduced, the field of view was narrow and there was no night vision. After the initial dose, the patient decided to abandon the quarterly maintenance dose because the regular dose may cause cataracts.
Significant improvement in a “micro” dose
After a single injection of Sepofarsen, more than a dozen measurements of visual function and retinal structure were performed, and the results showed great improvements, supporting the biological effects of the treatment. The key finding of this case is that the absorption of this biological effect is relatively slow. The researchers found that vision had improved after one month, but the patient’s vision reached its peak after the second month. Most strikingly, the improvement was still there when tested within 15 months after the first and only injection.
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Researchers believe that the durability of vision improvement is unexpected and offers the possibility of treating other ciliated diseases. Ciliopathy is the name of a large group of diseases related to mutations in genes encoding defective proteins, which can lead to abnormal cilia function, that is, the protrusion of sensory organs. Found on the cell.
“This work represents a truly exciting direction for RNA antisense therapy. It has been 30 years since the emergence of new drugs that use RNA antisense oligonucleotides, although everyone is aware that these treatments are very useful. Great hope,” Jacobson said. “The unexpected stability of the ciliary transition zone in patients has prompted people to reconsider the dosing regimen of Sepofarsen and other cilia-targeted therapies.”
Researchers say that one of the reasons why antisense oligonucleotides have been shown to be successful in treating this rare disease is that these tiny RNA molecules are small enough to enter the nucleus, but they are not cleared very quickly, so they stay for a long time. Long enough to complete their work. the work.
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For future research, Penn authors are planning gene-specific therapies for other blinding inherited retinal diseases that are currently incurable.
Source: Pennsylvania Medicine
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