Safety and Efficacy of Autologous iNSC-DAP in the Treatment of Parkinson's Disease

Study Overview
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Brief Summary
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This is a phase I, interventional, single arm, open-label, clinical study to evaluate the safety and efficacy of the striatal transplantation of autologous induced neural stem cell-derived DA precursor cells in Parkinson's Disease patients.

Detailed Description
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Parkinson's Disease (PD) is the second most common neurodegenerative disease, caused by progressive depletion of midbrain dopaminergic neurons in the substantia nigra pars compacta. This clinical study will include the preparation of dopaminergic neural precursor cells derived from neural stem cells through reprogramming of patient's peripheral blood mononuclear cells (PBMCs), and transplantation of the obtained cells into the brains of PD patients by stereotaxic injection. Safety, tolerability, evidence of cell survival (using PET scan), and the efficacy on PD symptoms will be assessed at different time points up to 12 months post-transplantation.

Official Title
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Safety and Efficacy of Autologous Induced Neural Stem Cell-derived Dopaminergic Precursor Cells in the Treatment of Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Autologous induced neural stem cell-derived DA precursor cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages between 30 and 85 years, males or females; Diagnosed to be Parkinson's disease patients according to MDS Parkinson's disease diagnostic criteria; Disease history over 3 years; Hoehn and Yahr Stage less than or equal to 4 during the medication on time; Responsive to levodopa treatment (Maximum rate of improvement in MDS-UPDRS, part 3, is over 30%). Exclusion Criteria: Atypical Parkinsonian syndrome or secondary Parkinsonian syndrome; Accompanied with other central nervous system diseases; With other severe systemic diseases or dysfunction; With severe psychiatric disorders; Subjects are using hormone or cytotoxic drugs and cannot stop taking the drug during the trial; With cognitive disorders (MMSE<24); With severe dyskinesia (MDS-UPDRS part 4, score in 4.1/4.2 ≥ 2); Subjects have undergone previous brain surgery; Subjects are long-term user of anticoagulant; Subjects have intracranial lesions which may affect the surgery or follow-up studies as assessed by imaging; Subjects are unable to undergo MRI or AV133 PET examination; Pregnancy or in preparation for pregnancy; Not suitable to participate in this clinical trial as assessed by the study investigators/physicians.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous induced neural stem cell-derived DA precursor cells<br>The patients will receive transplantation of autologous induced neural stem cell-derived DA precursor cells. | Drug: Autologous induced neural stem cell-derived DA precursor cells<br>* The autologous induced neural stem cell-derived DA precursor cells will be stereotactically implanted into the striatum of PD patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of changes during the medication off time in Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), part III, in comparison with baseline values. | Minimum score: 0; Maximum score: 132; Higher scores mean a worse outcome. | Within 12 months post-transplantation | 
| Incidence and severity of transplant-related adverse events. |  | Within 12 months post-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of changes in Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), part I, in comparison with baseline values. | Minimum score: 0; Maximum score: 52; Higher scores mean a worse outcome. | Within 12 months post-transplantation | 
| Assessment of changes in Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), part II, in comparison with baseline values. | Minimum score: 0; Maximum score: 52; Higher scores mean a worse outcome. | Within 12 months post-transplantation | 
| Assessment of changes in Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), part IV, in comparison with baseline values. | Minimum score: 0; Maximum score: 24; Higher scores mean a worse outcome. | Within 12 months post-transplantation | 
| Assessment of changes during the medication off time in motor function by using Purdue Pegboard test and gait analyzer, in comparison with baseline values. |  | Within 12 months post-transplantation | 
| Assessment of changes in the daily total medication off time in comparison with baseline values. |  | Within 12 months post-transplantation | 
| Assessment of changes in Unified Dyskinesia Rating Scale in comparison with baseline values. | Minimum score: 0; Maximum score: 104; Higher scores mean a worse outcome. | Within 12 months post-transplantation | 
| Assessment of changes in daily levodopa-equivalent dose in comparison with baseline values. |  | Within 12 months post-transplantation | 
| Assessment of changes in Parkinson's Disease Questionnaire (PDQ-39) in comparison with baseline values. |  | Within 12 months post-transplantation | 
| Assessment of changes in AV133 PET imaging in comparison with baseline values. |  | Within 12 months post-transplantation | 
| Assessment of changes in International Parkinson and Movement Disorder Society - Non-Motor Rating Scale (NMSS), in comparison with baseline values. | Minimum score: 0; Maximum score: 960; Higher scores mean a worse outcome. | Within 12 months post-transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous; iNSC; DA precursor cells; Parkinson's Disease; Cell therapy; Stereotaxic injection