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Alzheimers Dement. 2014 Feb;10(1 Suppl):S38-46. doi: 10.1016/j.jalz.2013.12.005.

Exenatide as a potential treatment for patients with Parkinson's disease: first steps into the clinic.

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Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK. Electronic address:
Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK.



There is an increasing number of approaches to try and relieve the motor symptoms of Parkinson's disease (PD) that focus predominantly on strategies of dopaminergic replacement or deep brain stimulation. There remains, however, a major need to slow down or reverse the relentless progression of the disease to prevent the evolution of disabling motor and nonmotor features that continue to cause disability despite the existing symptomatic approaches. Data emerging from the laboratory suggest that agonists for the glucagonlike peptide 1 (GLP-1) receptor may have biological properties relevant to PD pathogenesis and progression.


Future progress in the evaluation of GLP-1 agonists such as exenatide as potential disease-modifying treatments in PD can be facilitated by collection of proof-of-concept data to mitigate against the risk associated with major financial investments into these agents. There are, nevertheless, multiple issues that must be considered in the planning, setup, and conduct of pilot trials of potential disease-modifying drugs.


Open-label proof-of-concept data have been collected in a small cohort of patients with moderate severity PD that suggest that this agent is well tolerated. Patients randomized to receive exenatide showed advantages on validated motor and nonmotor scales of PD that persisted after a 2-month drug washout period.


Although data must be interpreted with caution, given the strong possibility of placebo effects, the clinical evaluation of these patients supports additional investment into double-blind trials of the GLP-1 agonists in PD.


Clinical trial design; Exenatide; Exendin 4; GLP-1; Parkinson's disease

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