A phase I/II trial run by the Dutch company ProQR has found that its RNA therapy could significantly improve the vision of people with Leber’s congenital amaurosis, a rare genetic disease for which there is no treatment. 

The RNA drug, called sepofarsen, is designed to treat people with a specific mutation in a gene called CEP290. This mutation causes the RNA transcript of the gene to have the wrong three-dimensional structure, blocking its translation into a protein. This, in turn, causes vision loss in the first few years of life. 

Sepofarsen is an RNA molecule that specifically binds to the faulty RNA transcript to stabilize its structure and allow the retinal cells to produce the protein. 

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In a phase I/II trial run in the US and Belgium, the RNA drug significantly improved the vision of children and adults with this condition over a 1-year period. 

“In some cases the patient’s vision improved to a level that could be deemed life-changing,” said Stephen Russell, a professor at the University of Iowa and principal investigator of the study. 

The effects of the drug were stronger on patients that had a certain level of visual acuity to start with. These are ultimately the target population of ProQR, which is already running a phase II/III study that will follow the response of 30 patients over the course of 2 years. Results from that trial are expected in 2021 and will inform whether the FDA and the EMA approve the drug or not.

The main goal of the phase I/II trial was to determine the safety of sepofarsen. While the treatment caused cataracts in eight out of 11 patients, all of those who underwent lens replacement surgery recovered their vision. Other side effects of the drug on the eye were manageable with additional treatments. 

There are hundreds of different genetic mutations that cause blindness. The rarity of each of these conditions individually has meant that many of them have no treatment available. In recent years, gene therapy has become an option to treat some of these conditions; the first was Luxturna, approved in 2017. Another approach that has only entered the first clinical trial this year is CRISPR gene editing, which is being carried out by Editas Medicine and Allergan.

In contrast, ProQR’s RNA drug could provide an alternative approach that does not involve a permanent change in the DNA of retinal cells. The drug is instead delivered to the eye via injection every 6 months. 

Still, each of these new treatments can only address one specific mutation of the many causing blindness. As all these new technologies are developed, together they could eventually provide solutions covering a wide range of these mutations.

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