Another trial in the promising GLP-1 receptor agonist cohort and co-funded by The Cure Parkinson's Trust and the Van Andel Institute through the Linked Clinical Trials initiative, this study will evaluate the effect of the diabetic drug lixisenatide versus placebo on the progression of motor disability in people with early Parkinson's in order to assess its potential disease-modifying effect.

The study is being conducted in France and is a multicentre 2-arm, randomised, placebo-controlled, double-blind, 'proof-of-concept' phase II trial.

Several mechanisms including the aggregation of misfolded alphasynuclein, mitochondrial dysfunction, oxidative stress and neuroinflammation have been related to the way in which the condition develops termed the pathogenesis of Parkinson's. Recent evidence further suggests the implication of cerebral insulin resistance in the neurodegenerative process, while glucagon-like peptide 1 receptor (GLP1-R) agonists that are approved for the treatment of type 2 diabetes have neuroprotective properties in animal models of PD (Aviles-Olmos et al., 2013a). Moreover, the results of a recent clinical pilot trial suggest that treatment with the GLP-1R agonist exenatide for 12 months improves motor function in people with moderate Parkinson's. GLP-1 receptor agonists are widely expressed in the central nervous system and drugs such as liraglutide, lixisenatide and exenatide have measurable brain concentrations, which makes them suitable for treating Parkinson's.

Lixisenatide is a well-tolerated GLP-1R agonist that can be administered by injection once-daily. It has previously demonstrated positive effects on learning and memory in preclinical models. Furthermore, lixisenatide increases neurogenesis and decreases microglial activation (the first and main form of active immune defence in the central nervous system) in rodent models. At the same dose, lixisenatide showed higher effectiveness at activating brain GLP-1R than liraglutide and exenatide, and showed more effective neuroprotection in a variety of in-vitro models of neurodegeneration. 

This randomized, double-blind, clinical trial now aims to assess the effects of lixisenatide, versus placebo, on both motor and non-motor symptoms in people with early stage Parkinson's.

For further information: https://clinicaltrials.gov/ct2/show/NCT03439943

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Contact: Olivier. RASCOL, MD, PHD 05 61 14 59 62 ext 33 [email protected]
Contact: Wassilios MEISSNER, MD, PHD 05 57 82 12 53 ext 33 [email protected]