Neurological damage, vision defects, have always been known to be irreversible. But a body of evidence contradicts that notion as a wonder drug–mutation-specific RNA therapy–has been reported to reverse the blindness caused by a rare genetic disorder.
Hope for reversing blindness
Leber congenital amaurosis [LCA] is a rare genetic eye disorder that appears at birth or within the early months of birth. It affects vision to varying degrees, and can sometimes lead to blindness. In addition, there could be nystagmus and loss of eye reflexes.
The culprit mutations have over 18 types, but type LCA caused by CEP290 mutation is one of the most important causes.
Essentially, this mutation causes abnormal growth and development of photoreceptor cells. This abnormality translates to different degrees of visual impairment.
An important discovery made by scientists at the Scheie Eye Institute [in the Perelman School of Medicine at the University of Pennsylvania] was that this intraocular injection of an RNA therapy caused major changes in the fovea [point of clearest vision]. The recovery of vision could be a result of such changes. The findings from these clinical trials were published in Nature Medicine.
With that knowledge, they tested their theories on humans. A patient from Penn Hospital Medicine with Leber Congenital Amaurosis recovered vision for about a year after receiving this single-dose intraocular RNA therapy–Sepofarsen.
Seeing the results, co-lead author Artur V. Cideciyan, Ph.D. [research professor of Ophthalmology] remarked, “Our results set a new standard of what biological improvements are possible with antisense oligonucleotide therapy in LCA caused by CEP290 mutations… importantly, we established a comparator for currently-ongoing gene-editing therapies for the same disease, which will allow comparison of the relative merits of two different interventions.”
Simply put, the working principle of Sepofarsen, which is an antisense RNA oligonucleotide, elevates the levels of normal CEP290 protein in the photoreceptors of the eye. This in turn markedly boosts the vision as the international clinical trial led by Drs. Cideciyan and Samuel G. Jacobson revealed
In addition to this body of evidence, a 2019 study conducted by Cideciyan, Jacobson et al revealed that repeated doses of Sepofarsen every three months resulted in improved visual function and retinal structure in 10 patients tested. The vision peaks after about two months. Even after 15 months, these improvements remained.
The therapy owes a huge of chunk its success to the minute size of its antisense RNA oligonucleotide. Their small sizes enable them to cross into cells quite easily and they are slowly cleared, which means they are afforded enough time to act.
This research shows that all hope is not lost for those with blindness secondary to a genetic defect. It also provides the blueprint for other ciliopathies that may cause blindness.
Dr. Jacobson corroborates by saying “This work represents a really exciting direction for RNA antisense therapy. It’s been 30 years since there were new drugs using RNA antisense oligonucleotides, even though everybody realized that there was great promise for these treatments,”
Without a doubt, there is hope for treating blindness. The drug, Sepofarsen, may still be in the experimental phases, but once the trials have successfully ended, it will be nothing short of a ‘miracle’.