August 08, 2017
By Anne Harding
NEW YORK (Reuters Health) – The diabetes drug exenatide improves off-medication motor scores in Parkinson’s disease patients, and these improvements persist for several weeks after drug discontinuation, a new single-center clinical trial shows.
“We’re very excited about this research, and I think it’s an important step in the right direction,” Dr. Dilan Athauda of the University College London Institute of Neurology in the UK, the study’s lead author, told Reuters Health by telephone. “We think this class of drugs may be important in the future of Parkinson’s disease treatment, but we really need to replicate these results and see if they can be replicated in a larger population.”
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The findings were published in The Lancet, online August 3.
Exenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved by the US Food and Drug Administration in 2005 for treating type 2 diabetes. Preclinical studies have found neuroprotective effects of exenatide, and a small study by Dr. Athauda and his team found improvements in motor and cognitive function in Parkinson’s patients after 12 months on the drug compared to placebo. The improvements persisted for 12 months after patients stopped taking the drug.
In the new study, the researchers randomly assigned 62 patients to exenatide or placebo for 48 weeks (in additional to their usual medication), followed by a 12-week washout period.
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At 48 weeks, patients’ off-medication scores on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 had improved by 2.3 points, whereas they had deteriorated by 1.7 points in the placebo group, for a significant adjusted between-groups difference of -4.3 points. At 60 weeks, scores were 2.1 points lower than baseline in the placebo group, and 1.0 point higher than baseline with exenatide, for a significant between-groups difference of 3.5 points.
“This is the largest indication we have that this drug could be affecting the underlying disease itself rather than symptoms, but it’s important to remain cautious,” Dr. Athauda said. He noted that the 3.5-point difference observed in the study was unlikely to be noticeable to patients. Nevertheless, he added, this is the largest benefit yet seen for any placebo-controlled clinical trial of medication for Parkinson’s.
Side effects, similar to those seen in patients taking exenatide for diabetes, included injection-site reactions and gastrointestinal system disturbances.
GLP-1 inhibitors appear to activate survival pathways in brain cells to help them function more efficiently, while reducing inflammation, Dr. Athauda said. He noted growing evidence that neurons can become resistant to the effects of insulin, and suggested drugs like exenatide may counter this effect.
He and his colleagues are now planning a larger multicenter clinical trial of exenatide in Parkinson’s patients.
Baseline imbalances between the study groups, including older age, higher MDS-UPDRS part 3 scores, and lower total levodopa-equivalent doses for the exenatide group - and the lack of between-groups differences in secondary outcome measures - are among the caveats raised by Dr. Werner Poewe and Dr. Klaus Seppi of Medical University Innsbruck in Austria in an accompanying editorial.
Nevertheless, they conclude: “Whether exenatide acts as a novel symptomatic agent or has neuroprotective effects on the underlying Parkinson’s disease pathology remains unclear, but Athauda and colleagues’ study opens up a new therapeutic avenue in treatment of Parkinson’s disease.”
SOURCES: http://bit.ly/2wt46FG and http://bit.ly/2vdtJMF
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