Choroideremia is one of the many forms of retinitis pigmentosa (RP). RP is an inherited disorder. It results from harmful changes in any one of the genes that carry the instructions for making proteins that are needed in cells (photoreceptors) within the retina – the light-sensitive tissue at the back of the eye.
The Photoreceptors are cells in the retina that begin the process of seeing by absorbing and converting light into electrical signals. Then the signals are sent to other cells in the retina and ultimately through the optic nerve to the brain. That is where they are processed into the images we see.
There are 3 different cases of RP, all of which result in damage to the photoreceptors:
- The mutations within the genes are so severe that the gene cannot make the required protein thus limiting the photoreceptors function.
- The mutations produce a protein that is toxic to the photoreceptors.
- The mutations lead to an abnormal protein that doesn’t function properly.
In the early stages of RP, people experience night blindness and a progressive loss of the visual field – the area of space that is visible at a given instant without moving the eyes. In the late stages of RP people lose more of the visual field, developing tunnel vision. RP is considered a rare disorder affecting an estimated 1 in 4,000 people. The symptoms normally appear in childhood.
Choroideremia has been considered untreatable, until now…
A single gene injection improved the vision for patients suffering from Choroideremia upon completion of a first gene therapy trial at Oxford University in the UK. The study and its positive results from a Phase 1/2 trial of NSR-REP1 were published in Nature Medicine in 2018. The ophthalmologist who led the trial, Professor Robert Maclaren, said he was very optimistic about the potential of the treatment.
“The early results of vision improvement we saw have been sustained for as long as we have been following up these patients. The trial has made a big difference to their lives.” – Maclaren
The trial involved 14 participants with Choroideremia. They all received an injection of healthy genes into the back of the eye. Out of the 14 patients, 12 either experienced significant gains of more than one line in the eye chart or had no further deterioration of their vision during the five years of the trial.
The success of this first study has led to a larger, international, gene therapy trial that will be conducted by Nightstar Therapeutics; this time involving over 100 patients. Nightstar is a clinical-stage company with the mission to maintain and restore sight in patients with inherited retinal diseases. Without treatment, these patients would otherwise progress to blindness. They explain why the eye is an ideal organ for gene therapy:
“The eye is an excellent target organ for gene therapy due to its accessibility, small size, compartmentalization and relative immune privileged status. The vectors can be directly injected into the diseased tissue and non-invasively observed for efficacy and safety. The blood-ocular barrier in the eye prevents the widespread dissemination of locally administered vectors throughout the body. Given the small volume of the eye, the amount of vector needed to achieve a therapeutic effect is low, reducing the amount of vector required to be administered to the patient and reducing potential systemic side effects.”
This groundbreaking discovery could pave the way for hundreds of thousands of people around the world to regain eye-sight.