Phase I/II Study of the Safety, Efficacy and Dose Evaluation of ProSavin for the Treatment of Bilateral Idiopathic Parkinson's Disease

Inclusion criteria

• Willing and able to give written Informed Consent
• Diagnosed with bilateral idiopathic PD
• Diagnosis of PD > five years, using diagnostic criteria from core assessment program for surgical interventional therapies CAPSIT (1999)
• Males/females between 48 and 65 years
• Women must be postmenopausal, with last menstrual period being over two years ago
• Male patients must agree to use at least two methods of contraception for at least 3 months following ProSavin administration if they and their partner is of child-bearing capacity
• Response to L-DOPA where an increase in dose is unacceptable to the patient due to potentiating the fluctuations in motor functions
• Hoehn and Yahr stage 3 and 4
• UPDRS (Part III) of between 20 and 60 in the "OFF" state
• Stable dosing of PD medication, including L-DOPA, for six weeks prior to surgery
• Positive response to dopaminergic therapy as defined by a 50% improvement in UPDRS (Part III) between the "OFF" and "ON" states
• Presence of motor fluctuations
• Willing to have current treatment withdrawn for up to 24 hours prior to surgery therefore being in an "OFF" state for surgery
• Willing to have their L-DOPA dosage reduced/withdrawn at the discretion of the principal investigator (PI) at regular intervals following surgery to allow assessment of ProSavin in the absence of concomitant anti-{Parkinsonian medication
• Affiliated with the French social security health care system (Patients enrolled in France only)

Exclusion criteria

• Major surgery within the 28 days prior to enrolment
• Severe disabling dyskinesias > or = 51% of the day as defined by the UPDRS (Part IV)
• History of psychosis or current treatment with dopamine blocking agents of any kind
• Severe depression as defined by a BDI score of >16. Any treatment for depression should be limited to seretonergic therapies and those that do not target the dopaminergic pathways
• Prior treatment with tolcapone within the six months prior to enrollment into the study, due to its ability to modify dopaminergic pathways in the brain
• History of epilepsy or any other co-morbid condition that the Investigator believes presents an unacceptable health risk to the patient in conjunction with the procedures in this protocol
• Life-threatening illness unrelated to PD
• History of stereotactic or other surgery for the treatment of PD
• Premenopausal women
• Alcohol or other substance abuse
• Clinically significant laboratory test abnormalities, including full blood count, chemistry panel, liver function tests, electrocardiogram (ECG), Chest X rays
• Any contraindication for undergoing an MRI scan of the head
• Intercurrent illness or infection 28 days prior to enrolment
• Abnormal MRI findings such as mega cisterna, septum pellucidum, signs of severe cortical or subcortical atrophy, brain tumours, vascular diseases, trauma or arteriovenous malformations (AVM)
• Prior regular exposure to neuroleptic agents
• History of treatment with any agent that may induce PD or PD symptoms within the last three months prior to enrollment
• Contraindications to use of anaesthesia
• Treated with dopaminergic antagonists six months prior to screening
• Concurrent antiretroviral therapy that would inactivate the investigational agent
• History of any investigational agent within 28 days prior to ProSavin administration
• Participation in a prior gene transfer therapy study
• Enrolment in any other clinical study, for any condition, including those relating to PD, throughout the duration of the ProSavin study
• Current of anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery
• Diagnosis of multiple systems atrophy (MSA) following assessment of the autonomic nervous systems function (e.g. blood pressure, difficulty in urinating and sexual activity) and MRI during the screening process
• Administration of subcutaneous rescue remedy apomorphine
• Patient unable to adhere to their prescribed Parkinson's disease treatment regime.