3 April 2024

Results from a one-year, phase 2 clinical trial of the Type 2 diabetes drug lixisenatide suggest that the treatment may slow the progression of motor symptoms in Parkinson’s disease. The study is published on 4 April in The New England Journal of Medicine and supported by Cure Parkinson’s and Van Andel Institute through the International Linked Clinical Trials programme.

About the trial:

The LixiPark study involved 156 people who had been recently diagnosed with Parkinson’s. Participants were treated with either lixisenatide or a placebo in addition to their usual Parkinson’s medication. The results of the randomized, double-blinded study showed that the progression of motor symptoms in those receiving the lixisenatide treatment slowed, while motor symptoms in participants receiving the placebo continued to progress. The difference between the two groups was statistically significant, indicating that lixisenatide may be able to delay the progression of motor symptoms in people with Parkinson’s.The findings were consistent at the end of the 12-month treatment period and two months after treatment stopped.

Led by Professors Olivier Rascol and Wassilios Meissner at the University Hospital of Toulouse and University Hospital of Bordeaux, respectively, the LixiPark trial involved 21 different research centres of the NS-Park Network across France. The study, sponsored by the Toulouse University Hospital, was co-funded by UK charity Cure Parkinson’s, with Van Andel Institute (VAI; in Michigan, US), and the French Ministry of Health, with drug and placebo support from pharmaceutical company Sanofi.

Lixisenatide was prioritised for clinical testing through Cure Parkinson’s and VAI’s International Linked Clinical Trials (iLCT) programme, an initiative that brings together leading Parkinson’s experts and advocates to prioritise potentially disease modifying treatments for clinical evaluation. Many of the drugs prioritised by the iLCT Committee have been approved to treat other conditions.

About GLP-1R agonists:

Lixisenatide belongs to a group of medicines called glucagon-like peptide 1 receptor agonists (or GLP-1R agonists) that work by mimicking the action of a natural gut hormone that is produced after eating food. This gut hormone stimulates insulin release from the pancreas, which helps cells in the body to absorb glucose that is eventually turned into energy. GLP-1R agonists are clinically approved for the treatment of Type 2 diabetes.

The LixiPark clinical trial results are important as they represent the second clinical trial of a drug in this class that has demonstrated a positive outcome on motor symptom progression in people with Parkinson’s at phase 2.[1] The first GLP-1R agonist to show potential to slow the progression of motor symptoms in Parkinson’s is exenatide, another iLCT prioritised drug currently being evaluated in large-scale, phase 3 clinical testing. Results from the exenatide trial are expected in 2024. There is a known link between Parkinson’s and Type 2 diabetes, with research suggesting that people with Type 2 diabetes have a higher risk of developing Parkinson’s.[2] Insulin resistance is common among people with Parkinson’s, and individuals with Parkinson’s who are Type 2 diabetic often experience a more rapid progression of their symptoms.[3] It has also been reported that people with diabetes who are treated with GLP-1R agonists have a reduced risk of developing Parkinson’s.[4]

Next steps:

While these results show exciting potential, further testing is required before this drug can be approved for clinical use in Parkinson’s. This phase 2 study has laid excellent groundwork for future testing, and Cure Parkinson’s is working with the investigators to plan the next phase of development.

It is important to note that there are a wide range of subtle differences between the broader class of GLP-1R agonists and they have not all been tested in Parkinson’s. Some GLP-1R agonists do not cross the blood brain barrier very well, and therefore are not able to affect the brains of people with Parkinson’s. More research is required to better 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 said:

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 Lixipark phase 2 trial showing less progression of motor symptoms of Parkinson’s disease over a year constitute a significant step forward in the future management of the disease. We look forward to confirming these encouraging results in the future, in order to  translate such findings into clinical practice.”

Dr Simon Stott, Director of Research at Cure Parkinson’s, said:

This is a very encouraging result for us here at Cure Parkinson’s. Along with our funding partners at Van Andel institute, we have been championing the repurposing of GLP-1 receptor agonists for Parkinson’s since 2010. This is the second phase 2 clinical trial indicating that this class of diabetes drugs is doing something interesting in Parkinson’s. We congratulate the investigators who conducted this study, and we are truly grateful to the participants and their families for helping to advance the research into disease modifying therapies for Parkinson’s.”

Dr Richard Wyse MBE, Director of Clinical Development at Cure Parkinson’s, added:

I am thrilled to see the extremely positive, groundbreaking clinical outcome of the lixisenatide trial, which could have real meaning for people living with Parkinson’s. Cure Parkinson’s originally identified lixisenatide as a potential treatment and has been championing and supporting this work, prioritising it for trial through our International Linked Clinical Trials programme. It has been a great pleasure working with the investigators, and we look forward to future clinical developments as we continue to pursue this exciting field of disease-modifying therapeutics to help treat Parkinson’s disease.”

Dr Darren Moore, Chair of Van Andel Institute’s Department of Neurodegenerative Science and a member of the iLCT Committee, said:

Today’s findings are a promising step forward in our exploration of GLP-1 receptor agonists as potential ways to slow or stop Parkinson’s progression. This important work would not be possible without collaboration and a shared commitment to finding therapies that impede Parkinson’s and improve quality of life. We are deeply grateful to our partners, the trial investigators and the trial participants and their families.”

[1] Rhee, Sang Youl., Han, Kyung-Do et al., Association between glycemic status and the risk of Parkinson Disease: A nationwide population-based study, Diabetes Care, Sep 2020,. https://pubmed.ncbi.nlm.nih.gov/32611610/ and Deischinger, C and Dervic, E et al., Diabetes Mellitus is associated with a higher relative risk for Parkinson’s Disease in women than in men, Journal of Parkinson’s Disease, April 2021., https://pubmed.ncbi.nlm.nih.gov/33492248/

[1] Athauda, D., Evans, J., et al., The impact of type 2 diabetes in Parkinson’s Disease, Movement Disorders, June 2022. https://pubmed.ncbi.nlm.nih.gov/35699244/

[1] Brauer, R., Wei, L., et al., Diabetes medications and risk of Parkinson’s disease: a cohort study of patients with diabetes, Brain, October 2020., https://pubmed.ncbi.nlm.nih.gov/33011770/

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