Achromatopsia is an inherited disease that results in total color blindness. Those that have it see only black, white, and grey. Their eyes are also susceptible to bright light, like the sun, and their vision blurs more the brighter it is.
It’s caused by mutations in one of six different genes. Most cases involve variants in either the CNGB3 or the CNGA3 genes (1/3 have the defect in the CNGA3 gene).
Pingelapese islanders have a mutation in the CNGB3 gene. They are people from a tiny atoll in the Pacific called Pingelap, also known as Color Blind Island. While achromatopsia is rare – affecting about 1 in 30,000 people worldwide – as many as 10% of the people who live on this Eastern Caroline Island of Micronesia have it.
How is this possible? In 1780 a tsunami struck the island of Pingelap and nearly wiped out the entire population. Only the king and as little as 20 others survived. The story goes to say that the king had the genetic fault that causes achromatopsia, and he passed it on to many descendants. Due to the remoteness of the island and a culture that frowns upon marriage to outsiders, the gene pool has remained tight, allowing for the mutation to persist.
Although many there are afflicted, it is in Germany that a team of researchers from the Institute for Ophthalmic Research in Tübingen and LMU in Munich has developed a treatment to help its people with the condition. About 3,000 people have achromatopsia in the country. The team developed a new gene therapy to correct the defect in the CNGA3 gene and conducted the first human clinical trial with successful results. Until now, there has been no treatment available for the condition.
There was a separate gene therapy (conducted by a different team of scientists) that went through a clinical trial for choroideremia, a form of inherited total blindness. In that study, a single injection to the back of the eye improved the vision for 12 out of the 14 patients.
The treatment for achromatopsia and the one for choroideremia work similarly. In both cases, a healthy functioning gene is attached to a genetically modified harmless virus, and the treatment is injected directly into a patient’s eye. The aim is for the proper functioning gene to begin producing the protein that wasn’t being made by the defective gene. The missing protein was the cause of the condition.
In the new trial for achromatopsia, nine patients linked to variants in CNGA3 participated, and the procedure proved to be safe with minor improvements in vision.
Dominik Fischer, head of the clinical study, said:
The experimental subjects suffered no drug-related health problems as a result, nor did their retinas show any permanent changes.
Stylianos Michalakis, another author on the study, said:
Since the gene vectors used have proven to be safe, a follow-up study in pediatric CNGA3 patients is possible and useful.
The next trial will likely involve children. For safety reasons, this first one recruited only adults. However, the procedure is less effective in adults because the retinas have already fully developed. Now that the team knows the treatment is safe, they will test the gene therapy on very young patients with higher brain plasticity and retinal tissue that hasn’t fully developed yet to truly gauge the success of the treatment in curing color blindness.
Professor Marius Ueffing, the Director of the Institute for Ophthalmic Research in Tübingen, explained:
Furthermore, the parts of the brain that process vision increasingly lose plasticity in adulthood. Since the brains of people with achromatopsia have never learned to process color information, they need at least some plasticity to translate the retina’s newly acquired ability to respond to colors into a real visual impression.
Professor Bernd Wissinger of the Tübingen Research Center for Ophthalmology added:
The study is an important first step. It represents a milestone on the road to a curative therapy of achromatopsia, and we expect even better treatment success in the future.
The follow-up study will likely involve patients younger than seven because, beyond that age, the visual cortex has mostly developed, and structural loss of cone photoreceptors has taken place. The next trial has already been approved, and they will use the vector in both eyes.
