Exendin-4 as a Treatment for Parkinson's Disease - Pilot Study

Inclusion Criteria: * Diagnosis of Idiopathic Parkinson's disease of moderate severity- equivalent to Hoehn/ Yahr stage 2 to 2.5 (Bilateral symptoms but still physically independent). Male or female. Female patients to be post menopausal (defined as 12 months of spontaneous amenorrhoea or 6 months spontaneous amenorrhoea with FSH levels greater than 40mIU/ml), surgically sterilised (post hysterectomy and/or oophorectomy). Male patients with female partners that have child bearing potential must use adequate contraception (condoms +/-spermicidal gel/foam) throughout the duration of the trial period. * Age 45-70 years * Disease onset after age 40 years * Disease duration \> 5 years * On L-dopa treatment. Patient must be on oral L-dopa treatment - with or without dopamine agonist including Apomorphine, MAO-B inhibitor, COMT inhibitor, Amantadine, Beta blocker, anticholinergic treatment History of wearing off phenomena- duration of action of single dose of L-dopa \< 6 hours Stable PD medication for preceding 3 months- i.e. no change in medication type or dose. * UPDRS motor off medication score \>15 * L-dopa responsiveness. Defined as \>33% improvement in UPDRS motor off medication score following L-dopa challenge * Able to give informed consent * Able to comply with trial protocol and willing to attend necessary clinic visits off medication. Exclusion Criteria: * Diagnosis or suspicion of other cause for parkinsonism including Vascular parkinsonism, post traumatic parkinsonism, drug or toxin induced parkinsonism, or other neurodegenerative condition including Multiple System Atrophy, Progressive Supranuclear Palsy, Huntington's disease, Wilson's disease, Pantothenate kinase Neurodegeneration (PKAN), Alzheimer's disease, Creutzfeld Jacob disease. * Known abnormality on CT or MRI brain imaging considered to be causing symptoms or signs of neurological dysfunction, or considered likely to compromise compliance with trial protocol. Concurrent dementia defined by a score lower than 120 on the Mattis Dementia Rating Scale. * Concurrent severe depression defined by a score greater than 16 on the MADRS Exposure to neuroleptic drugs within 6 months prior to baseline assessment Prior intracerebral surgical intervention for Parkinson's disease including Deep Brain stimulation, lesional surgery, growth factor administration, gene therapy or cell transplant * Already actively participating in a trial of a device, drug or surgical treatment for Parkinson's disease, or trial participation within previous 30 days. * Type 1 Diabetes mellitus * Type 2 Diabetes mellitus on insulin treatment * End stage renal disease or severely impaired renal function with creatinine clearance \<30ml/min * History of severe cardiac disease (Angina, Myocardial infarction or cardiac surgery in preceding 2 years) * History of pancreatitis * History of alcoholism * Severe gastrointestinal disease including gastroparesis * Ongoing treatment with sulphonylurea * Females that are pregnant or breast feeding or of child bearing potential.