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Could Exenatide improve non-motor symptoms?
Original article:What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson’s Disease: A Post Hoc Analysis, The Journal of Parkinson’s Disease: May 19, 2018.
While the original clinical trial of exenatide for Parkinson’s focused primarily on movement, an exploratory analysis into non-motor symptoms has indicated it could improve mood and emotional wellbeing. These results fall within a range which would be meaningful to people with Parkinson’s and will inform the design of future clinical trials, which would establish whether these effects are statistically significant.
Why is it important?
Non-motor symptoms are part and parcel of Parkinson’s, but effective treatments for these are yet to be developed. These preliminary findings indicate that exenatide may be conferring some benefits on these symptoms, which can be directly investigated in subsequent clinical trials.
- Novelty 75% 75%
- Proximity 100% 100%
- Deliverability 97% 97%
“This study provides new evidence that exenatide can benefit non-motor symptoms of Parkinson’s in addition to the already reported benefit to motor symptoms. This adds to the urgency of a multi-centre clinical trial for this GLP-1 agonist.” – Dr Tilo Kunath
Exenatide is an anti-diabetic drug which was shown to slow down the progression of movement symptoms in Parkinson’s in a recent clinical trial. Since non-motor symptoms such as mood, sleep problems, apathy, thinking difficulties and autonomic problems (eg., constipation) are also part of Parkinson’s, questionnaires assessing these more globally were also administered. 60 people with moderate Parkinson’s were assigned to one of two treatments (placebo, exenatide), which they received over a period of 48 weeks, completing regular assessments of their motor and non-motor symptoms. They were followed up for another 12 weeks after the end of treatment in order to examine whether benefits were sustained. Although clear improvement was seen on exenatide compared to placebo in terms of movement (as assessed using the UPDRS), no statistically significant improvements were seen on the questionnaires used to assess non-motor symptoms and quality of life. But did exenatide really have no effect in this respect?
Since the questionnaires which addressed non-motor aspects of Parkinson’s target several different symptoms which are then grouped together into a sum total, a more fine-grained analysis was performed. Could any improvements actually be detected on individual symptoms, such as mood, apathy, emotional wellbeing, cognition, sleep/fatigue and autonomic problems? Due to the nature of this exploratory analysis, it could not reveal statistically significant improvements but it could address changes which might be meaningful to people with Parkinson’s, in other words remarkable from the perspective of their experience. Such improvements were seen on mood and overall emotional wellbeing while on exenatide. Importantly, these benefits were independent of changes seen in movement related symptoms. It is not yet clear whether these improvements in non-motor symptoms were the result of exenatide halting the progression of Parkinson’s itself, or the result of exenatide acting independently on the brain. Basic research into the effects of exenatide has shown that it can, in itself, reduce behaviours linked to anxiety and depression in rodents, so more research is necessary.
These early indications are useful in informing the design of a future clinical trial with more participants, where more specific non-motor symptoms could be targeted in order to reveal any true, statistically significant effects.
Two further phase 2 clinical trials using similar drugs, Liraglutide and Lixsenatide are currently underway. Both these drugs also activate the GLP-1 receptor and are currently used to treat type two diabetes, preclinical evidence has suggested that these drugs may have a more potent and longer lasting effect than Exenatide in models of Parkinson’s. More information about these trials can be found on the CPT website.
Original article: AAthauda D, Maclagan K, Budnik, N, Zampedri, L, Hibbert S, Skene, SS, Chowdhury, K, Aviles-Olmos I, Limousin P, Foltynie T. May 19, 2018. What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson’s Disease: A Post Hoc Analysis, The Journal of Parkinson’s Disease