Recent research on the type 2 diabetes drug lixisenatide reveals its potential to mitigate the progression of motor symptoms in patients with Parkinson’s disease. This discovery was made possible by a year-long Phase 2 study, details of which have been published in The New England Journal of Medicine, and which has received support from Cure Parkinson’s and the Van Andel Institute (VAI) through the International Linked Clinical Trials (iLCT).
The LixiPark trial involved 156 individuals recently diagnosed with Parkinson’s who were given lixisenatide or a placebo, in addition to their usual Parkinson’s medication. Findings from the study, which was randomized and double-blind, indicate that those treated with lixisenatide experienced a slowing in the progression of their motor symptoms, in contrast to those receiving placebo, whose symptoms continued to progress.
The observed difference was statistically significant, suggesting that lixisenatide could be able to postpone motor deterioration in people with Parkinson’s. These results were consistent after 12 months of treatment and were maintained even two months after its completion. Lixisenatide was selected for clinical trials thanks to Cure Parkinson’s and VAI’s iLCT program, which seeks to evaluate treatments with the potential to modify the course of the disease, bringing together Parkinson’s experts to prioritize therapies for clinical evaluation.
A new advance in the treatment of Parkinson’s disease
Lixisenatide is one of the GLP-1R agonist drugs that mimic the action of a natural intestinal hormone that is produced after eating, stimulating the release of insulin from the pancreas. This helps cells absorb glucose to convert it into energy and has been approved to treat type 2 diabetes.
The results of the LixiPark trial are significant as they represent the second phase 2 study that demonstrates a positive impact on the progression of motor symptoms in patients with Parkinson’s using this class of medications, after the potential demonstrated by exenatide, another drug prioritized by the iLCT that It is currently being tested in a Phase 3 trial.
A relationship between type 2 diabetes and Parkinson’s has been established, suggesting that people with type 2 diabetes have a higher risk of developing Parkinson’s. It has also been observed that treatment with GLP-1R agonists reduces the risk of developing Parkinson’s in diabetics.
Despite the potential shown, further testing is required before lixisenatide can be approved for clinical use in Parkinson’s. This Phase 2 study lays the foundation for future research, and Cure Parkinson’s is collaborating with researchers to plan the next stage.
“The results of the LixiPark trial demonstrate a positive impact on the progression of motor symptoms in patients with Parkinson’s using GLP-1R agonist medications”
It is crucial to note that there are subtle differences between GLP-1R agonists, not all of them have been evaluated in Parkinson’s. Some do not cross the blood-brain barrier well, which limits their ability to act in the brains of people with Parkinson’s, and more studies are needed to understand these differences in the context of a potential treatment for Parkinson’s.
Professors Wassilios Meissner and Olivier Rascol, principal investigators of the study, jointly stated: “For 30 years, we have been trying to understand how to slow the decline associated with Parkinson’s disease over time. In this context, the positive results of the phase 2 LixiPark trial, showing a reduced progression of the motor symptoms of Parkinson’s disease in one year, constitute an important step forward in the future treatment of the disease. “We hope to confirm these encouraging results in the future, so we can translate them into clinical practice.”
Side effects of the antidiabetic lixisenatide and limitations of the study
José Luis Lanciego, Senior Researcher of the Gene Therapy Program in Neurodegenerative Diseases at the Center for Applied Medical Research (CIMA), University of Navarra, who has not participated in the study, stated in statements to SMC Spain: “The most relevant finding is that after 12 months of treatment the score on the motor scales is 3 points lower in the treated patients compared to the patients in the placebo group. The clinical scale used is the so-called MDS-UPDRS III, which the higher the score indicates the greater the severity.”
“Although the 3-point improvement is not very striking, it is statistically significant. However, it is necessary to consider whether this improvement is sufficiently beneficial on a clinical level, since it presents various side effects such as nausea, vomiting and gastroesophageal reflux (present in 46%, 13% and 8% of patients treated with the drug, respectively). , gastrointestinal side effects already commonly reported in diabetic patients treated identically. Note that side effects were considered unacceptable in approximately one-third of patients treated with lixisenatide, so it was necessary to reduce their maintenance medication (20 micrograms) to the starting dose (10 micrograms).”
“Among the limitations of the study, it is necessary to take into account that all patients are treated with antiparkinsonian medication of various kinds during the clinical trial, so it is difficult to evaluate whether the modest beneficial effect obtained with lixisenatide is due to said drug or to the antiparkinsonian medication itself. It is also necessary to take into account that the follow-up time is relatively short (12 months) to correctly evaluate whether or not lixisenatide has a long-term effect. Furthermore, only the dosage regimen recommended for the treatment of diabetes mellitus has been used, without considering other dosages.”
“In conclusion, and as the authors themselves recognize, it will be necessary to carry out clinical trials with a larger number of patients and with a longer period of time to correctly determine the efficacy and safety of this potential reuse treatment for parkinsonian patients.”
