Gene Therapy Restores Cone Function of Colour Blind Youngsters

gene therapy

According to a study by University College London, gene therapy partially restored the function of the retina’s cone receptors in two youngsters. Moreover, both of them were born colour-blind, completely.

The findings were published in the journal Brain. They suggest that the treatment is efficiently stimulating previously dormant communication pathways between the retina and the brain. Furthermore, it is taking advantage of the plasticity of the developing adolescent brain.

Phase 1/2 Clinical Trial

The academic-led investigation has operated concurrently with a phase 1/2 clinical trial in children with achromatopsia. It is also employing a novel method to determine whether the medication is altering the brain pathways. Especially for cones.

Achromatopsia is caused by disease-causing mutations in a few genes. It affects cone cells, which are a type of photoreceptor in the eyes. The other type is rods. People with achromatopsia are completely colourblind since cones are important for colour vision. Additionally, they also have very poor eyesight overall and photophobia as well. Their cone cells do not send messages to the brain. However, plenty of them remain, so researchers have been looking for ways to revive the dormant cells.

Lead Author Tessa Decker said,

Our study is the first to directly confirm widespread speculation that gene therapy offered to children and adolescents can successfully activate the dormant cone photoreceptor pathways and evoke visual signals never previously experienced by these patients.

We are demonstrating the potential of leveraging the plasticity of our brains, which may be particularly able to adapt to treatment effects when people are young.

The study was conducted among four kids and teenagers with achromatopsia between the ages of 10 and 15 years. Professor James Bainbridge at UCL and Moorfields Eye Hospital was the main researcher of the study.

The two studies evaluated gene treatments targeting specific genes known to cause with achromatopsia. Furthermore, each study targets a different gene. Their major goal of the study is ensuring the safety of the procedure. In addition, also evaluating for improved vision. However, their findings have not yet been fully collated. Therefore, the total effectiveness of the treatments is still not known.

The academic study that accompanied it used a novel fMRI mapping approach to separate emerging post-treatment cone signals from existing rod-driven signals in patients. This enabled the researchers to directly attribute any changes in visual function after treatment to the targeted cone photoreceptor system. They used a “silent substitution” technique with pairs of lights to excite cones or rods selectively. The researchers also had to modify their methodology to account for nystagmus, which is another sign of achromatopsia. Researchers compared the findings to the 9 untreated patients and 28 healthy volunteers.

Gene Therapy

Each of the four children received gene therapy in one eye, allowing doctors to compare the treatment’s efficacy to that of the untreated eye.

6 to 14 months following treatment, there was substantial evidence for cone-mediated signals in the brain’s visual cortex originating from the treated eye in 2 of the 4 youngsters. The patients had no evidence of cone function on any testing prior to therapy. Following therapy, their measurements matched those of the study’s normal-sighted subjects.

Participants in the study also took a psychophysical test of cone function, which measures the ability of the eyes to discern between different levels of contrast. This demonstrated a difference in cone-supported vision between the treated eyes of the identical two youngsters.

Effectiveness of the Treatment

The researchers state that they cannot establish whether the treatment was ineffective in the other two trial participants, whether there were treatment effects that were missed by the tests utilized, or whether effects were delayed.

The co-lead author said,

In our trials, we are testing whether providing gene therapy early in life may be most effective while the neural circuits are still developing. Our findings demonstrate unprecedented neural plasticity, offering hope that treatments could enable visual functions using signalling pathways that have been dormant for years.

We are still analyzing the results from our two clinical trials, to see whether this gene therapy can effectively improve everyday vision for people with achromatopsia. We hope that with positive results, and with further clinical trials, we could greatly improve the sight of people with inherited retinal diseases.

Dr. Dekker further added,

We believe that incorporating these new tests into future clinical trials could accelerate the testing of ocular gene therapies for a range of conditions, by offering unparalleled sensitivity to treatment effects on neural processing, while also providing new and detailed insight into when and why these therapies work best.

Moreover, the participants of the study commented,

Seeing changes to my vision has been very exciting, so I’m keen to see if there are any more changes and where this treatment as a whole might lead in the future.

It’s actually quite difficult to imagine what or just how many impacts a big improvement in my vision could have, since I’ve grown up with and become accustomed to low vision, and have adapted and overcome challenges (with a lot of support from those around me) throughout my life.


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