Between science fiction and biblical miracle

Three of their four children will go blind for the rest of their lives: parents, Edith Lemay and Sébastien Pelletier, trying to make the most of their sad fate. The Canadian family is currently traveling the world so their children can still see and experience as much as possible.

That’s because Mia (12), Colin (7), and Laurent (5) suffer from hereditary retinitis pigmentosa, which causes you to gradually lose your eyesight. His only son Leo (9) did not inherit the disease. The family started in Namibia, meanwhile the children learn to surf in Lombok in Indonesia and visit temples in Malaysia. Parents make the trip public on Instagram (@pleinleursyeux) and move the whole world with it. Mom wants to fill her visual memory with the best and most beautiful pictures. Because blindness cannot be prevented so far.

Hope for those affected by Switzerland

But there is hope: A clinical trial is currently underway in the US for a new type of drug that could stop and even reverse genetic degeneration of the retina. Behind him are the biotech company Endogena Therapeutics and Matthias Steger (52) of Zurich. “The tragedy of this disease is that you know you will go blind, but you don’t know how much time you have left,” says the biochemist. About one in 3000 people are affected in Switzerland – there are 1.5 million people worldwide. It begins with tunnel vision, followed by loss of contrast and color, and often ends with complete blindness. Photosensitive cells, that is, photoreceptors, gradually die.

What if the destroyed photoreceptors in the retina could be regenerated? Like a lizard tail that falls off and grows on its own? That’s exactly what they’re working on at Endogena Therapeutics in the Bio-Techno-Park in Schlieren ZH. Facilities with offices and labs are furnished with an abundance of light, color and design – in a poster magnified 2,000 times you can see what Steger and his team were working on: activated cones and rods in the eye’s cross-section. previously a blind mouse.

scientific sense

The recording documents a scientific sensation. “To date, no one has shown that photoreceptors can be reproduced in the adult mammalian eye,” says Steger. This kind of regeneration takes place spontaneously in our body, often without paying much attention to these processes. When old cells die, body cells regrow in organs such as the heart and liver, or in tissues such as skin, cartilage, or muscle. Skin cells completely renew themselves within a month. Other cells, such as in the eye, do little or nothing: “If the photoreceptors in the retina are damaged, they cannot regenerate themselves.”

When Steger began his career at F. Hoffmann-La Roche over 20 years ago, he was involved in the design and synthesis of active molecules for a variety of therapeutic indications. The biochemist has a steep career in the multinational pharmaceutical company, most recently as head of global research and technology partnerships. For Steger, who got up at 5 a.m. and went for a jog to work on a race bike, at one point the traditional pharmaceutical industry was no longer agile enough: “I saw the opportunities offered by this new method against degenerative diseases. I can be more dynamic with my own company.”

Mice can see again

The idea behind the drug therapy called EA-2353: Eye stem cells are “awakened” from their dormant state by appropriate molecules. Over the years, the researcher has built up his own library of 2,000 molecules for Endogena Therapeutics: “They are the most important currency in our industry, major pharmaceutical companies have over a million test substances.” Molecules are like keys that unlock the biological pathway and thus regulate it. Finding the right one to develop an effective therapeutic is detective work. “It’s like looking for a needle in the famous haystack. This is possible thanks to artificial intelligence and faster data analysis,” says the researcher. Only after a few thousand tests does a hit appear, a so-called hit.

In this way, Endogena Therapeutics has identified, further developed and tested in the first step approximately 20 active molecules in vitro. “We showed that we can activate retinal stem cells in the test tube,” Steger says. This approach has been successfully tested on blind mice. Steger: “Several tests show that mice can see again!”

The clinical trial on 14 blind patients will be completed next summer. If all goes well, it will take at least three years for the EA-2353 to hit the market. Since the method does not reverse the genetic defect, the substance injected into the eyeball needs to be reapplied regularly. Hope is high: “We get up to 20 requests a day from those affected,” says Steger.

Research for vision

Endogena Therapeutics isn’t the only biotech company to explore the battle against blindness. Other clinical trials in the field of retinitis pigmentosa are also ongoing. Christian Grimm (60) observes research efforts in this area. “Many of these work with gene and stem cell therapies and optogenetics,” says the professor, Head of Research at the University of Zurich Eye Clinic. The second is based on the knowledge that even bacteria and algae with special proteins can detect light. A virus acts as a “taxis” to smuggle the genetic blueprint of light-sensitive proteins into diseased retinal cells. In one case study, a previously blind patient was able to recognise objects, but he needed glasses specially developed for this purpose. “For a blind person, even small steps mean improvement,” says Grimm.

Science has yet to perform the biblical miracle of the blind man’s sight again. “Right now there are many approaches. Most won’t work, but it will be a breakthrough method,” Grimm was convinced. Teams in many labs are investigating the use of the body’s own stem cells, which are then returned to the eye as reprogrammed cells. But this is a long and complex process: “Cells must first be taken from the patient, then reprogrammed and differentiated. All this is under absolutely sterile conditions,” Grimm explains.

Leading to degenerative diseases

Were Canadian children able to protect their eyes with this method? As a scientist, Matthias Steger doesn’t want to make any guesses without providing evidence: “The treatment is probably successful in younger patients, that is, before degeneration of the retina begins.”

If the method works, it could be groundbreaking for the treatment of dementia, muscle weakness or other degenerative diseases such as osteoporosis. The next clinical trial is currently underway at Endogena Therapeutics, specifically on age-related macular degeneration, or AMD for short, which is the most common cause of blindness from the age of 50. Steger: “Modern medicine has solved many problems, so we age. But not the ailments associated with it.” Endogenous regenerative medicine is a new approach: “We work with the body, not against it.”