At a special press event on April 26th, science magazine, two scientists specializing in GLP-1 receptor agonists answered journalists' questions via video conference. Most of the questions were about diabetes and obesity. These drugs revolutionized the treatment of these two epidemic diseases and changed society's relationship with hunger, diet, and food. While these drugs face supply problems due to their huge demand, they exhibit some interesting side effects. “In recent years, we have learned that Ozempic has an impact on diseases such as Alzheimer's disease and Parkinson's disease,” said Lotte, chief scientific advisor for research and early development at Nordisk, the Danish company that makes Ozempic and Novo. Bjerre Knudsen says. “It's all hypothetical, but it's important to emphasize that progress is being made and it's very positive.”
Recent clinical trials published in New England Medical Journal, supports this idea. The study points out how Parkinson's disease patients treated with the diabetes drug lixisenatide maintained their motor skills without significant changes for a year.
“Thanks to the clues that epidemiology left us, we started our investigation,” Olivier Lascol, a neurologist at the University of Toulouse and lead author of the study, explained in a video call. People with type 2 diabetes have a higher risk of developing Parkinson's disease than other people. This is a trend that has been pointed out in various studies. “On the other hand, we found that diabetic patients treated with this type of drug, GLP-1, had a lower risk of developing Parkinson's disease than those who received other antidiabetic drugs,” the authors explained. do. So they started an investigation.
The study began in 2014 with 156 patients recruited during the early stages of the disease. Half received lixisenatide for 12 months. The rest received a placebo. This last group was then found to develop more severe symptoms of Parkinson's disease by 3 points (on a scale that measures how well they can perform tasks such as talking, eating, and walking). Patients treated with lixisenatide remained stable.
These three differences are related, but not dramatic. “It's a small change,” assesses Álvaro Sánchez Ferro, a neurologist at the 12 de Octubre Hospital in Madrid, Spain, and coordinator of the Movement Disorders Research Group of the Spanish Society of Neurology. “It would be almost imperceptible to the human eye. A five-point change would be enough to say that something had a more or less substantial effect.” Interestingly, Dr. Sanchez, who was not involved in the study, said: Dr. Ferro points out that this is a validation of this neuroprotective effect. And the game-changer is to see if this 3-point gap continues to grow over the years.
“It's a million dollar question… no, it's a ten million euro question,” quips Vasilios Meissner, professor of neurology at Bordeaux University Hospital. Meissner, who participated in the study, is cautious. “That's what we want, but we need to prove it. If you treat it for 10 years and the final effect is 3 points, you can decide it's not worth treating. But , increasing that to 5 or 10 points would make a clear difference and would be very helpful.”
What is important with this treatment is not just what to achieve, but how to treat it – to get to the root of the problem. “Parkinson's disease is a neurodegenerative disease in which different areas of the brain are damaged and neurons are lost,” explains Dr. Sánchez-Ferro. “This affects many areas, but particularly the nigrostriatal pathway associated with motor control.” The disease destroys the cells that produce dopamine, which is reflected in a person's movements. They become increasingly slow and uncoordinated. Until now, drugs such as levodopa, used for Parkinson's disease since the 1960s, artificially increased dopamine production.
“The effects of GLP1 agonists are quite different,” Professor Rascol says. “They prevent the neurons that produce dopamine from dying. In other words, it's like you have a pool and you're losing water in it. There are two ways to deal with this problem. Either you add water to maintain the water level (which is what levodopa does), or you try to find where the leak is and where the water is escaping, which is what we are accomplishing with lixisenatide. In any case, experts note that while this treatment may stop or slow neuron loss, it cannot in any case restore lost neurons. Emphasize. The effects of Parkinson's disease are irreversible.
But how do drugs designed for diabetes have a neuroprotective effect on the brain? “We know that insulin receptors are also present in the brain,” Meissner says. “They are very important for regulating glucose levels in the blood and in various organs. But they are also involved in the survival of neurons.” When a person has Parkinson's disease, these receptors are It starts to malfunction. “In these regions, we see abnormalities that are reminiscent of insulin resistance. Abnormalities similar to those that occur in diabetes.”
GLP-1 agonists not only act in the gut, but also in the brain. Lixisenatide is one of the first generation drugs in this family and one of the drugs with the greatest effects at the neuronal level. Cristóbal Morales, an endocrinologist at Virgen de la Macarena Hospital, said: “It is no longer used in diabetes. It's medicine,'' he says. and Vitas Hospital (both in Seville, Spain) and members of the Spanish Obesity Society. “But its neuroprotective effects are very good.” Morales points out that this is something that has been suspected for years. “Large clinical trials involve a lot of quality-of-life questionnaires, and we're starting to see that this drug improves markers of cognitive impairment.” It's the first time we've made that connection, and it's the first step in demonstrating what the various studies are suggesting. But we have a long way to go.
Work has already begun. GLP-1 receptor agonists have been shown to not only reduce inflammation in the liver, kidneys, and heart. These drugs also appear to be effective in reducing inflammation in the brain, leading scientists to hope that these compounds could be used to treat not only Parkinson's disease, but also other neurodegenerative diseases such as Alzheimer's disease. are doing. Both are characterized by inflammation of the brain.In a recent review published in a scientific journal, Naturelists more than 20 clinical trials in which the drug is being studied as a treatment for both diseases.
What is clear so far is that although two very different diseases are related, there may be a common solution. “It's important to get treatment,” says neurologist Sánchez Ferro. “But also talk about how to avoid Parkinson's disease. And in this case we need to emphasize the importance of physical exercise. Sports have been proven to be protective at the neurological level.”
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