AAV2-GDNF for Advanced Parkinson s Disease

This is an interventional treatment trial for Parkinson's Disease focused on measuring Gene Therapy, Parkinson's Disease, Convection-Ehanced Delivery, Viral Vector Read More

• INCLUSION CRITERIA:

Greater than 18 years of age.

Diagnosed with Idiopathic PD.

• Bradykinesia and
• At least 3 of the following clinical features: resting tremor, cogwheel rigidity, bradykinesia, postural reflex impairment.

The above clinical features must not be due to trauma, brain tumor, infection, cerebrovascular disease, other known neurological disease (e.g., hereditary form of PD, multiple system atrophy, progressive supranuclear palsy, striatonigral degeneration, Huntington s disease, Wilson s disease), or to known drugs, chemicals or toxicants.

Disease duration of > 5 years.

Hoehn and Yahr Stage III or IV off medication.

Disability present despite optimal antiparkinsonian medication therapy. Disability will be operationally defined as a Modified Schwab and England Activities of Daily Living Scale score of 80% or lower (during the off state).

Unified PD Rating Scale (UPDRS) (Fahn et al., 1987) total motor score greater than or equal to 30 in the defined off state.

Unequivocal responsiveness to levodopa, based on the single-dose levodopa test (as described in the CAPIT and CAPSIT guidelines). A 30% or greater improvement in the UPDRS total motor score will be required to establish unequivocal responsiveness to levodopa.

Able to provide proper Informed Consent.

Laboratory values at screening visit (unless other visit specified):

• Platelets >100,000/mm3 (transfusion independent)
• PT/PTT in normal range and INR less than or equal to 1.3 (on day prior to surgery, if taking anti-coagulants)
• Absolute neutrophil count (ANC) >1500/mm3
• Hemoglobin >10.0 g/dL (transfusion allowed)
• Aspartate aminotransferase or alanine aminotransferase <2.5 times ULN
• Total bilirubin <2.5 mg/dL
• Serum creatinine <1.5 mg/dL
• Serum anti-AAV2 total antibody titer <1000.

EXCLUSION CRITERIA:

Presence of prominent oculomotor palsy, cerebellar signs, vocal cord paresis,mean standing blood pressure below 75mmHg, pyramidal tract signs or amyotrophy.

Genetic PD disorders or with a strong family history of PD.

Presence of dementia (Montreal Cognitive Assessment less than or equal to 25).

Received an anti-dementia drug for treatment of cognitive impairment within 30 days of their screening for protocol eligibility.

Presence or history of psychosis, including if induced by anti-PD medications at doses required to improve motor symptoms.

Presence of untreated or suboptimally treated depression (Hamilton Depression Scale score >10) or a history of a serious mood disorder (i.e., requiring psychiatric hospitalization or a prior suicide attempt).

Presence of substance (drug, alcohol) abuse.

Contraindication to MRI and/or gadolinium.

Presence of normal striatal uptake on PET.

Coagulopathy, anticoagulant therapy, low platelet count, or inability to temporarily stop any antithrombotic medication.

Prior brain surgery, including GDNF, NTN, GAD, AADC therapy or deep brain stimulation.

Male or female with reproductive capacity who is unwilling to use barrier contraception throughout the study.

History of stroke or poorly controlled cardiovascular disease.

Uncontrolled hypertension or diabetes or any other acute or chronic medical condition that would increase the risks of a neurosurgical procedure.

History of malignancy (cerebral or systemic) other than treated cutaneous squamous cell or basal cell within the prior 5 years.

Clinically active infection, including acute or chronic scalp infection.

Received investigational agent within 12 weeks prior to screening.

Unable to comply with the procedures of the protocol, including frequent and prolonged follow-up.

Chronic immunosuppressive therapy (e.g., chronic steroids, TNF antagonists, chemotherapy)

Pregnancy or lactation.