AADC Gene Therapy for Parkinson's Disease

This is an interventional treatment trial for Parkinson Disease focused on measuring Adeno-associated virus, Aromatic L-amino acid decarboxylase, AAV-hAADC-2, AAV-2, Gene Therapy, Gene Transfer, Parkinson Disease, Basal Ganglia Disease, Brain Disease Read More

Inclusion Criteria:

1. Patients with idiopathic Parkinson's disease meet diagnostic criteria for Specified Disease designated by the Ministry of Health, Labour and Welfare (1995) : the Research Committee of CNS Degenerative Disease, L-Dopa is effective in the early disease stage and no findings suggestive of CNS Degenerative Disease are found.
2. Age ≤ 75 years at the time of medical treatment.
3. Age at onset ≥ 35 years.
4. Duration of L-dopa therapy ≥ 5 years.
5. Hoehn and Yahr Stage IV in OFF state at the onset of medical treatment.
6. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Scale Part III (MDS-UPDRS-III), minimum motor score of 30 to a maximum motor score of 100 in OFF state.
7. Positive response to dopaminergic therapy as evidenced by remarkable improvement in MDS-UPDRS-III motor score between the defined "OFF" and "ON" state: a minimum 16 points improvement in the MDS-UPDRS-III after dopaminergic therapy.
8. Patients who can undergo the stereotaxic surgery for Parkinson's disease due to the intolerable motor complication minimum score of 4 to a maximum score of 9 in the MDS-UPDRS-IV part B (diurnal fluctuation of symptom) , not responsive to optimal medical therapy.
9. To be able to comply with the requirements, including the frequent clinical examination after medical treatment, in this study.
10. To keep the therapeutic medicine for Parkinson's disease for at least 2 months prior to participation in this study.
11. Written informed consent.

Exclusion Criteria:

1. Patients who is suspected secondary / atypical parkinsonism based on the medical history of cerebral vascular disease, exposure to antipsychotic or toxic agents, and encephalitis or based on the symptom of Progressive supranuclear palsy, Pyramidal tract sign, autonomic sign, Dementia, Hallucination, Delusion and so on or based on the finding by magnetic resonance imaging (MRI) such as Lacunar infarct or atrophy of the midbrain tectum and atrophy of the pons and the cerebellum.
2. Patients with history of 3 hours or more of intensive or violent dyskinesias in the past 6 months.
3. Patients with previous the stereotaxy for Parkinson's disease (pallidotomy, thalamotomy, deep brain stimulation) .
4. Mini-Mental State Examination (MMSE) ≤ 20 or patient with a diagnosis of dementia in the neuropsychological evaluation.
5. Patients with medical history of Hallucination, Delusion, schizophrenia or affective disorder within 6 months of informed consent.
6. Patients with history of significant cardiovascular disease including cerebrovascular accident.
7. Malignant neoplasm in the brain, clinically significant neurological disease (for example significant brain atrophy not consistent with age).
8. History of other malignancy, with the exception of treated carcinoma cutaneum, within 5 years.
9. Uncontrolled hypertension: systolic blood pressure ≥ 160 mmHg.
10. Coagulopathy or need for anticoagulant therapy.
11. Clinically significant immune dysfunction (for example, the case who require the use of immunosuppressive drugs).
12. Geriatric Depression Scale (GDS) short scale ≥ 10 points, or if on antidepressant, the score > 5 points.
13. On monoamine oxidase (MAO)-A inhibitors, or antipsychotic medications.
14. Unable to scan MRI.
15. Cases without abnormal finding in FMT-PET.
16. Premenopausal female or male who desire impregnating a female (excluded: in case when sperm is cryopreserved prior to gene therapy and child is born by using the sperm).
17. Past medical history of convulsive seizure within 3 years or receiving antiepileptic drug or patients with epileptic aberrance in the electroencephalography.
18. Past medical history of serious drug allergy.
19. Patients who have participated in other clinical trial within 6 months.

20. Patients who meet any of the following criteria:

    1. Serious renal disorder ( Cr ≥ 2.0 mg/dl and BUN ≥ 25mg/dl)
    2. Serious hepatic disorder ( AST (GOT) / ALT (GPT) ≤2.5xupper limit of normal (ULN)
    3. Serious diabetes (casual blood glucose or fasting blood glucose ≥ 200 mg/dl and HbA1c ≥ 9 %)
21. Any other patients judged by investigators to be inappropriate for the subject of this study.