New research suggests that drugs used to treat insulin resistance could potentially help in treating neurodegenerative disorders like Parkinson’s disease. The study found that semaglutide, a compound found in medications like Ozempic, and a similar compound called DA5-CH reduced chronic inflammation in the brain and protected brain cells in animal models of the disease.
The study was published in the journal Parkinson’s Disease.
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, which means it mimics the action of the GLP-1 hormone in the body. By activating GLP-1 receptors, semaglutide helps regulate blood sugar levels, promotes insulin secretion, reduces appetite, and enhances weight loss.
Several studies have found a link between diabetes and an increased risk of developing Parkinson’s disease. The drugs previously tested in animal models and clinical trials include GLP-1 receptor agonists like exendin-4, liraglutide, semaglutide, and a novel dual GLP-1/GIP receptor agonist called DA5-CH, which was developed by the authors of the current study.
The new study aimed to investigate the potential neuroprotective effects of semaglutide and DA5-CH in Parkinson’s disease. Parkinson’s disease is a chronic neurodegenerative disorder characterized by the loss of dopamine-producing neurons in the brain, and the researchers wanted to determine if these drugs could protect against the loss of these neurons in a rat model.
“Drugs that originally were designed to treat diabetes have shown good protective effects in many different animal models of central nervous system diseases,” explained study author Christian Hölscher, a professor at the Henan University of Chinese Medicine and the chief scientific officer at Kariya.
“In this study, we tested one of these drugs that belong to the GLP-1 class in a rat model of Parkinson’s disease and compared it to a novel dual agonist drug that we developed and that can enter the brain much better than the drug semaglutide that has been developed to treat diabetes, not Parkinson’s disease.”
The researchers used a rat model of Parkinson’s disease induced by a neurotoxin called 6-OHDA. “This model recapitulates many pathological symptoms of Parkinson’s disease, including the death of dopaminergic neurons,” Hölscher said.
The researchers treated some of the rats with either semaglutide or DA5-CH, while others received a control treatment. To evaluate the effects of the drugs, the researchers measured several parameters. They looked at the rats’ motor behavior by assessing how well they moved and whether their circling behavior improved. They also examined the levels of dopamine, a neurotransmitter that is reduced in Parkinson’s disease, in the rats’ brains.
The results showed that both semaglutide and DA5-CH improved motor behavior, protected neurons, increased dopamine levels, reduced inflammation, and lowered levels of harmful forms of alpha-synuclein. This suggests the drugs could potentially be effective treatments for Parkinson’s disease.
“We show in this study that the drug was protective in this model, which is very encouraging,” Hölscher told PsyPost. “The take-home message is that these drugs are genuinely protective in the brain, and that we are not very far away from one of these drugs coming to the market as a drug treatment to slow down or stop Parkinson’s disease.”
“Our novel dual agonist is designed to treat Parkinson’s and works better than the GLP-1 class drugs that are on the market to treat type 2 diabetes. We are in phase 1 trials now with our drug, and hopefully can enter a phase 2 clinical trial next year.”
The researchers are hopeful about the potential of these drugs, especially DA5-CH, which was found to be more effective than semaglutide in the study. They believe that these drugs could slow down or halt the progression of Parkinson’s disease.
“It was good to see that our drug is working better than the older drug semaglutide,” Hölscher said. “Since three of these older drugs showed good effects in Parkinson’s patients already, and our drug is better than those drugs in animal models, we hope that it will be superior in the clinic, too.”
While the findings suggest that targeting insulin resistance with drugs like semaglutide and DA5-CH may hold promise as a new approach for treating Parkinson disease, further research and clinical trials are needed to confirm their effectiveness and safety in humans.
“The main question is always if the results from animal studies will translate into the clinic,” Hölscher told PsyPost. “Hopefully, we will see similar improvements in patients with Parkinson’s disease, but that needs to be tested.”
The researchers also emphasize the need for more awareness about these potential treatments, as many scientists still focus on a protein called alpha-synuclein, which forms abnormal clumps or aggregates called Lewy bodies. But clinical studies investigating treatments specifically targeting alpha-synuclein have not yet shown significant improvements in Parkinson’s disease patients.
“This research area is quite new, and surprisingly few people in research know about this,” Hölscher said. “We need to raise awareness that there is something out there that actually works. At the moment, many scientists believe that a protein called alpha-synuclein causes Parkinson’s disease.”
“However, clinical studies do not support that hypothesis. Two large phase 3 trials have shown no improvements at all when removing alpha-synuclein in the brain. It is high time to spread the word that GLP-1 type drugs actually help to reduce or stop disease progression in patients.”
The study, “DA5-CH and Semaglutide Protect against Neurodegeneration and Reduce α-Synuclein Levels in the 6-OHDA Parkinson’s Disease Rat Model“, was authored by Lingyu Zhang, Chun Li, Zijuan Zhang, Zhenqiang Zhang, Qian-Qian Jin, Lin Li, and Christian Hölscher.