Treating Blindness with Gene Therapy and Optogenetic therapy

You must have seen a lot of people who are blind, and when you ask if they were born blind, you get responses like they never saw anything since they knew themselves. Such cases can exist in lot of children who when giving birth to looked like they have good sight, only to see that they begin to develop symptoms such as eyes moving involuntarily and not being able to gaze at people. This type of symptom can be associated with conditions such as Leber Congenital Amaurosis which is a congenital disease.

Leber Congenital Amaurosis (LCA) is a condition caused by genetic changes or mutations which causes visual impairment and could lead to people getting permanently blind from childhood. It is very unfortunate to say that just like LCA, there are lots of disorders that cannot be cured but then some scientists have been working to change this, so people can be able to see again.

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According to the article "Partial recovery of visual function in blind patient after optogenetic therapy", scientist tried to cure eye diseases using optogenetics and gene therapy. gene therapy is a branch of research that can revolutionize modern medicine and is required to treat genetic disorders as the name implies.

Genetic disorders are diseases which are caused by defects in genetic structures which are often referred to as mutations. When an egg cell is fertilized by sperm cells, the DNA of the mother and father combines. While this goes smoothly, in rare cases, we can experience mutations and sometime the genetic instructions could be inherited by the gene. In the case of LCA, it is a rare genetic condition that occurs in 1 out of 40 thousand newborns with mutations in about 22 genes being associated to it.

With LCA, photorecptors from the retinal pigment epithelium aren't produced which mean that Rods and Cones cells do not receive the information they need, leading to the malfunction of the rods and cones causing them not to be able to receive light, leading to blindness. With gene therapy, the mutated gene is repaired or made intact. With LCA, the gene that is not functional would be replaced with an intact version causing the photoreceptors to be functional again. While it sounds easy, it is very difficult to perfect in reality. First, naked genes cannot be inserted into the body as they will be destroyed, so they need to be packed in vehicles which contains non-viral or viral parts.

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Another problem will be putting the gene in its targeted region. This is because the body contains billions of cells and most of them do not like to take up DNA but for LCA, the gene and vehicle are injected to the retina epithelium. Another concern is safety of the tissue, organ, and the individual. How do we inject the gene to be certain that it would be active throughout the rest of the patient's life.

In the phase one trial, an intact version of RPE65 was injected into the eyes of patients, and most of them improved in sight a for about 2 years, while some didn't get at all. This is because there are about 22 genes associated with this condition, and will require lots of tests to identify the faulty gene. Optogenetics can be another way to find solution to blindness, where light is used to control nerve cells or neurons. Instead of bringing an intact version of a mutated gene with gene therapy, the protein ChrimsonR is introduced as it is a light sensitive protein that activates neurons.

While we are still looking at getting this procedures right, do you think it is the solution we are looking for? Do you think it will be able to give hope to congetital blind patients helping them to see?

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Reference

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https://www.nature.com/articles/s41591-021-01351-4
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239363/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756725/
https://www.frontiersin.org/articles/10.3389/fbioe.2019.00466/full
https://kids.frontiersin.org/articles/10.3389/frym.2017.00051
https://www.ucsfhealth.org/conditions/leber-congenital-amaurosis-lca
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392113/
https://rarediseases.info.nih.gov/diseases/634/leber-congenital-amaurosis