There are no approved disease-modifying drugs for Parkinson disease, a neurodegenerative condition that affects 2–3% of people aged ≥65 years. Accumulating evidence suggests that GLP1 receptor agonists — incretin mimetics that researchers first developed for the treatment of diabetes — may have neuroprotective properties. A first randomized, placebo-controlled trial of AstraZeneca’s GLP1 receptor agonist exenatide now provides further support for these agents as possible Parkinson drugs, researchers report in The Lancet. The team of academic researchers ran aphase II trial of exenatide in 62 Parkinson patients, looking at the drug’s effects on the 132-point Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part 3 motor function score. After 60 weeks, there was a statistically significant 3.5 point adjusted difference between the exenatide and the placebo groups. Both groups experienced injection site reactions and gastrointestinal symptoms as common adverse events. These findings are in line with a previous open-label trial of exenatide in Parkinson disease, run by the same researchers. “Whether this drug acts as a novel symptomatic agent, influences compensatory responses or behaviours, or has neuroprotective effects on underlying pathology is unclear, but there is a strong indication that GLP1 receptor agonists may have a useful role in future treatment of Parkinson disease,” they write. They add that the role of these drugs is also being explored in other neurodegenerative diseases, including Alzheimer disease, amyotrophic lateral sclerosis and multiple sclerosis. In a linked commentary, neurologists from the Medical University Innsbruck call the
findings exciting but note several caveats. The baseline characteristics of the treatment and placebo groups were unbalanced; exenatide-treated patients tended to be older, for example, and had higher starting MDS-UPDRS part 3 scores. Exenatide-treated patients had greater increases in their concomitant use of dopaminergic therapy during the trial. And, the trial did not find significant improvements in any of the secondary outcome measures. The trial was funded by the Michael J. Fox Foundation for Parkinson’s Research. There are as yet no industry-sponsored trials of GLP1 receptor agonists in Parkinson disease. Earlier this year, a few companies advanced the first α-synuclein-targeted agents into phase II trials
Fonte: Nature Reviews Drug Discovery | Published online 1 Sep 2017 (Nat. Rev. Drug Discov. 16, 371–373; 2017).