Choroideremia is a rare inherited disorder that causes progressive loss of vision due to degeneration of the choroid and retina. Choroideremia is genetically passed through families by the X-linked pattern of inheritance. In this type of inheritance, the gene mutated in the disease (CHM) is located on the X chromosome. Carrier females are generally not affected by the disease but have a 50% chance of passing the mutated CHM onto their sons. Affected males will never pass the disease on to their sons, but their daughters will themselves become carriers.
This experimental gene therapy has been developed by a team led by Professor Robert MacLaren in the University of Oxford in the UK and is similar to gene therapy techniques for another rare inherited condition, Leber congenital amaurosis (LCA), that was first developed in Moorfields Eye Hospital in London in 2007. The gene therapy uses a small, safe virus to carry the missing CHM gene into the light-sensing photoreceptor cells in the retina. In an operation similar to cataract surgery, the patient’s retina is first detached and then the virus is injected underneath using a very fine needle.
The recent data from the ongoing clinical trial followed six patients for six months after treatment. The patients were a mixture of men with early stage and advanced choroideremia and treatment was in one eye to compare treated eye to untreated eye. After six months, the men with early stage choroideremia did not see any deterioration of their vision in their treated eye, and they will be followed up to see if this vision can be maintained. However, in the two men who had advanced choroideremia, the treatment has thus far surpassed expectations and these two men have gained two lines and four lines of vision on the eye chart. It is still early days for this trial, and monitoring the safety of this technology, as well as its effectiveness, will be the priority for the researchers over the coming years. You will find more information about the clinical trial at this link.
This is very encouraging news for Irish patients with inherited retinal degenerations. This is the first gene therapy that targets a gene expressed in the light sensing photoreceptor cells in the retina. It is also the first trial to have treated individuals who still have good vision. It therefore shows the potential of this type of therapy to be useful for other conditions such as retinitis pigmentosa and the dry form of age related macular degeneration and could potentially be used as an early intervention to arrest vision loss. From an Irish perspective, the Fighting Blindness backed Genable Technologies are currently developing a similar gene therapy approach for an autosomal dominant form of retinitis pigmentosa caused by mutations in the rhodopsin gene.
This form of targeted therapy is only possible by identifying the gene causing the condition, such as the CHM gene in choroideremia. This trial highlights the importance for individuals with inherited retinal diseases to identify which gene is responsible for their condition. Fighting Blindness have recognised this importance and are asking these individuals to take part in our Target 5000 project which aims to identify the estimated 5,000 individuals in Ireland with inherited retinal degenerations.
For more information about any of the above or to register for Target 5000, please contact our research officer on 01 6789 004 or firstname.lastname@example.org.