Currently, there is no treatment for color blindness, a genetic condition that affects color vision and affects millions of people worldwide. In recent years, gene therapy has made great strides in the hope of resulting in an effective treatment for disease. Harnessing the plasticity of the brain, researchers at University College London attempted an early gene therapy approach to activate cone cells in the retina of four children with total color blindness. Result: the therapy partially activated the dormant cones. A world first.
Depending on the people and the identity of the mutated gene, color blindness can manifest in different forms. In the case of achromatopsia where the disease is said to be “total”, it is caused by the mutation of particular genes and affects the conical photoreceptors of the retina, the latter being responsible for the perception of colours. People with total color blindness also have poor eyesight in general, photophobia (can’t stand bright light) and also something called nystagmus (involuntary eye wobble).
In these people, the cone cells are partially or completely inactive and send little or no signals to the neurons. As each of these cones is responsible for the perception of a specific range of colors, color blind people do not perceive colors or only poorly when these cells are inactive.
Namely that the hereditary disease has a greater prevalence in men than in women, because the mutation is carried by the X chromosome. And even if the majority of cases concern a benign form, it represents daily challenges for patients, who tend to be stigmatized and do not have access to certain activities and professions.
As the cone cells are present in each individual from birth, the therapeutic avenues against color blindness currently focus on the means of activating these cells, the latter being “dormant” in patients. Over the past few years, the feats of gene therapy have shown positive results in non-primate and primate modelsraising hope for clinical treatment.
The researchers in the new study then attempted to harness the plasticity of the developing brains of children with color blindness by giving them early gene therapy. In two children born with achromatopsia, cone receptors were partially activated, implying that processing may occur at the level of the neural pathway specific to these cells.
« We demonstrate the potential to harness the plasticity of the brain, which may be particularly able to adapt to the effects of treatment when people are young », Explain Tessa Dekker, lead author of the new study, which appeared in the journal Brain, and researcher in the department of ophthalmology at University College London. According to the expert, this study would be the first to confirm the widespread hypothesis that gene therapy administered to children and adolescents can successfully activate the pathways of photoreceptors in dormant cones, and allow visual signals never seen before in this type of patient.
Positive results on two out of four children
To test the new therapy, four children (10 to 15 years old) with color blindness participated in two different trials. Each targeting a specific gene, both trials targeted genes known to cause the disease. Using a functional MRI (fMRI) mapping approach, cone cell signals could be measured after treatment, to trace any changes in activity.
After administration of the treatments, the children’s eyes were stimulated with light sources that selectively targeted rod and cone cells. The subjects’ nystagmus was also taken into account. The results were then compared with those of nine untreated patients and 28 volunteers with normal vision. The four color-blind children only received the treatment in one eye, so that they could compare its effectiveness with the untreated eye.
In two of the sick children treated, signals emanating from the cone cells of the treated eye were observed 6 to 14 months after administration of the treatment. The activity of the cells was closely similar to that observed in healthy individuals, and this type of activity was never observed before taking the treatment in the patients concerned.
The participants also performed psychophysical tests assessing their eyes’ ability to perceive different contrasts and colors. Perception related to cone cells was significantly enhanced in the two aforementioned children.
In the two other color-blind children treated, the effectiveness of the therapy cannot be ruled out according to the researchers, because the effects could occur later. It is also possible that the tests carried out to detect an improvement in visual acuity are not sufficiently adapted. Moreover, all of the results have not yet been compiled. The real efficacy of the treatment should therefore be reassessed.