Gene therapy for AADC deficiency

JRCT ID: jRCTs033180309

Registered date:15/03/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Aromatic L-amino acid decarboxylase deficiency
• Date of first enrollment: 04/06/2015
• Target sample size: 8
• Study type: Interventional

Intervention(s)

Subjects will be hospitalized before Day -10and conducted the baseline examination. The target putmen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 200 micro L at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 micro L per site) at a flow rate of 3 micro L per minute on Day 0.
After the infusion is complete, the cannula devices will be removed, and the surgical incision will be seamed in accordance with usual trephination. After that, cranial CT scan will be performed so as to confirm whether there are complications such as the occurrence of intracranial bleeding or not. Subjects stay in a hospital for 14 days after infusion of AAV-hAADC-2.
Data and Safety Monitoring Board (DSMB) will be evaluated the efficacy of all subjects and safety of the treatment.
At the time of 6 months after the infusion, investigator assesses the treatment effect of AAV-hAADC-2 on the basis of clinical assessment and FMT-PET imaging.
The investigator also assesses the safety for 5 years after the baseline examination. Long-term follow up study is additionally conducted for 15years.

Outcome(s)

Primary Outcome

Safety of the method which AAV-hAADC-2 is injected into the putamen of patients with AADC deficiency.
Regarding adverse events, attack records, general physical findings, neurological findings, clinical examination, cerebrospinal fluid examination, brain MRI, electroencephalogram will be evaluated.

Secondary Outcome

Efficacy of AAV-hAADC-2 injection therapy.
Attack record, general physical findings, neurological findings,
Evaluate motor and cognitive function on evaluation scale
Clinical examination
Cerebrospinal fluid examination (including L-dopa, HVA, 5 HIAA)
Brain MRI, electroencephalogram
Expression amount of putaminal injection AAV-hAADC-2
FMT-PET: positron emission tomography using 6- [18 F] fluoro-m-tyrosine which is a tracer for AADC

Key inclusion & exclusion criteria

• Age minimum: >= 2age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1)Patients who have AADC deficiency with symptoms such as motor dysfunction and dystonia, and whose diagnosis has been confirmed by cerebrospinal fluid inspection findings, by enzyme activity measurement, or by genetic diagnosis.
2)Patients aged 2 years or older at the time of treatment.
3)Patients who do not show findings suggesting any other neurodegenerative disease.
4)Patients who are able to abide by the conditions essential for the research, including frequent medical examinations after the treatment.
5)Patients who have not changed any medications for at least 1 month prior to participation in this research.
6)Patients whose families have had a full explanation, have given their consent, and have signed the consent form.

Exclude criteria

1) Patients with cerebrovascular disease or other clear cardiovascular disease.
2) Patients who also have an intracerebral malignant neoplasm or other clinically evident neurological disorder.
3) Patients who have completed treatment for any malignant tumor other than skin cancer within the last 5 years.
4) Patients with high blood pressure (systolic blood pressure 160 mmHg or more).
5) Patients with blood coagulation disorder, or patients that require anticoagulant therapy.
6) Patients with a clinically evident immune disorder, or who require immunosuppressive agents.
7) Patients who cannot have MRI scans.
8) Patients in whom the generally recognized abnormal findings of AADC deficiency are not present on FMT-PET prior to the treatment.
9) Patients with a severe allergy to medication.
10)Patients who have taken part in a different clinical trial within the past 6 months.
11)Patients with severe liver disease, severe renal disease, or diabetes that is hard to control.
12)Patients with a serious general condition.
13)Patients who are otherwise judged by the overall director to be unfit to participate as subjects in the clinical research.

Related Information

• Primary Sponsor: Kojima Karin
• Secondary Sponsor: Shin-ichi Muramatsu
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED)
• Secondary ID(s): UMIN000017802