The patient, treated at the Casey Eye Institute in Portland, Oregon, belongs to a group of 18 people affected with Leber congenital amaurosis. These patients will participate in the BRILLIANCE study, the first clinical trial to determine the safety and efficacy of a therapy based on the CRISPR-Cas9 gene editing technique (AGN-151587, EDIT-101).
It is the first example of an in vivo CRISPR gene editing therapy, that is, administered directly into a patient’s body. So far, clinical trials have been performed with cells removed from patients, modified in the laboratory –ex vivo–and infused into their bodies for treatment. This approach had been applied to treat some types of cancer, sickle-cell anaemia and beta-thalassemia.
Developed by Editas Medicine, the AGN-151587 therapy has been designed to locate a fragment of the CEP290 gene that contains a mutation that causes Leber congenital amaurosis (c.2991+1655A>G in intron 26), and slice it out to restore normal gene function. The therapy involves injecting under the retina many copies of a modified virus containing all the molecular tools and instructions needed to “edit” the incorrect text and restore the production of the CEP290 protein.
The first patient was treated with a single injection into one eye. Within a few weeks, researchers will determine if the therapy has been effective and, in 2-3 months, evaluate improvements in patient’s vision. Onset of Leber congenital amaurosis occurs in childhood resulting in an irreversible form of blindness with no effective therapy until now. For another form of the disease, caused by mutations in the RPE65 gene, a specific gene therapy (Luxturna) has been developed, which has already been approved and is available in Europe and the United States.
It is hypothesized that the CRISPR editing modifies the patient’s genome permanently. If the expected accuracy and effectiveness is achieved, the CRISPR in vivo therapy approach will open up new, ultra-innovative perspectives on gene therapy for many other non-treatable pathologies of neuronal origin, which include the inherited eye disorders.
Image: OHSU performs first-ever CRISPR gene editing within human body. Author: Kristyna Wentz-Graff. Source via Wikimedia Commons under CC license.