RNA therapy for blindness
A clinical study conducted at the University of Pennsylvania showed the effectiveness of treatment developed for patients with Leber congenital amaurosis, an eye disease that primarily affects the retina and leads to severe visual impairment from early childhood. Leber's congenital amaurosis is often associated with a mutation of the CEP290 gene.
Specialists from the University of Pennsylvania organized an international study in which participants received injections into the vitreous body of an antisense oligonucleotide called sepofarsen. This is a short fragment of RNA that restores the normal level of the CEP290 protein in the photoreceptors of the eye and improves the functions of the retina in daytime vision.
Currently, a whole series of clinical trials is underway using antisense oligonucleotides to correct various genetic defects.
The authors found that injections of sepofarsen, repeated every three months, led to a steady improvement in vision in 10 patients. The eleventh patient, whose treatment was described in detail in this study, received only one injection and was monitored for 15 months. Before the start of treatment, the patient had decreased visual acuity, narrowed visual fields and impaired night vision. After the first injection, he decided to abandon the quarterly maintenance doses, as they increased the risk of cataracts.
After a single injection of sepofarsen, more than a dozen measurements of visual function and retinal structure showed significant improvements confirming the biological effect of the treatment. The researchers noted that the first changes were observed a month after the injection, the patient's visual acuity peaked two months later. The most striking thing is that the improvements persisted for 15 months of follow-up after the first and only injection.
The unexpected stability of the changes noted in the patient requires a review of the regimen of administration of sepofarsen, as well as other antisense RNA therapy drugs. Such a persistent improvement in vision is of great importance for the treatment of other ciliopathies – a category of diseases associated with genetic mutations that lead to abnormal cilia function on cells.
One of the reasons why antisense oligonucleotide has been so successful in the treatment of Leber congenital amaurosis is that short RNA fragments are small enough to get into the cell nuclei and are excreted slowly, remaining in the nucleus long enough to carry out their function.
For future research, scientists are planning gene-specific therapy for other currently incurable hereditary retinal diseases that lead to irreversible loss of visual functions.
Article A.V.Cideciyan et al. Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report published in the journal Nature Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: A single injection reverses blindness in patient with rare genetic disorder