Most cases of blindness today occur as a result of ageing or, in many fewer cases, due to physical trauma or accidents. But there are genetic causes that doom the sight of young people – and one of the rare disorders – but a terrible one – is retinitis pigmentosa (RP), which affects one in 4,000 people. Unfortunately, it is one of the most common forms of inherited retinal degeneration, with between 2,000 and 3,000 patients living in Israel.
Initial symptoms include reduced peripheral vision and difficulty seeing at night. As side vision worsens, people may experience blurring, slow adjustment from dark to light environments and vice versa, blurring of vision and “tunnel vision.” Although it is rare for RP victims to go completely blind, the vision problems often begin in childhood and gradually get worse by age 30.
A result of the progressive loss of rod photoreceptor cells in the back of the eye (retina) followed by loss of cone photoreceptor cells, RP is caused by mutations in one of more than 50 genes.
There is currently no cure for the disorder, but patients could be helped by the use of portable lighting, low-vision aids or orientation and mobility training.
The progressive nature of and the lack of a cure for retinitis pigmentosa contribute to the inevitably discouraging outlook for patients with this RP.
Israeli researches, however, are now offering RP patients some hope. Researchers from the Blavatnik Institute for Drug Development at Tel Aviv University (TAU) and Sheba Medical Center at Tel Hashomer (in Ramat Gan near Tel Aviv) are developing what they believe could be an effective treatment of RP.
A clinical trial about a decade ago found that a natural food supplement extracted from algae improved the vision of about a third of patients, but over time the effectiveness of the treatment became unstable due to ecological changes in the composition of seaweed, whose growth was hurt by changing temperatures and currents in bodies of water. The algae stopped producing the substance naturally in sufficient quantities.
The Israeli team members were able to develop a synthetic substance that mimics the natural substance 9-cis-β-carotene extracted from seaweed. The new development will make possible the production of the active ingredient in the required quality, quantity and concentrations, resulting in the continuation of continuous and effective treatment.
The researchers at the Blavatnik Institute, which specializes in the development of drugs for rare diseases, included Prof. Ehud Gazit, Dr. Elvira Haimov and Dr. Ludmilla Buzhansky. Together with Dr. Ygal Rotenstreich and Dr. Ifat Sher at Sheba Medical Center.
The researchers explain that retinitis pigmentosa is a genetic disease, caused by mutations that prevent the body from absorbing beta-carotene – an essential pigment for vision, found in orange vegetables such as carrots. As a result, a degenerative process of the retina occurs, the patient’s field of vision decreases, to complete and inevitable blindness, usually at a young age.
About a decade ago, a clinical trial was conducted in which 29 patients with retinitis pigmentosa were treated with a natural food supplement extracted from algae containing the active ingredient C9 beta-carotene – a version of beta-carotene that is absorbed into patients, bodies despite the mutation. The treatment improved the condition of about a third of the patients in key parameters – night vision, field of vision and electrical activity in the retina.
Haimov, head of the medical chemistry unit at the Blavatnik Center explained that “due to changes in the composition of the seaweed grown naturally, we realized that the solution to the problem is to produce a reliable and stable synthetic drug. The main challenge in the development process was the fact that the active substance 9-cis-β-carotene is not chemically stable; it decomposes easily in the presence of light and oxygen. This situation makes the production processes very difficult, and the shelf life of the material is also very short.”
“To solve the problem, they developed conservation methods, mainly by adding stabilizers. “We are currently in the upscaling phase, with the goal to make possible the production of the material in larger quantities,” said Haimov.
Buzansky, who directs the Blavatnik Center added that “the drug we have produced has been successfully tested on retinal neuron cultures, and we now seek to produce a sufficient amount of material. This will allow us to advance to the further laboratory and mouse experiments and then human clinical trials. Since this is a material that has been proven in the past to be effective and safe in its natural form, we are very optimistic about the potential effectiveness of the synthetic material we produce. We believe it will serve as a basis for the development of an effective drug that will address a significant percentage of patients with retinitis pigmentosa and save their eyesight,” she concluded.
