Mesenchymal Stem Cells Transplantation to Patients With Parkinson's Disease

Study Overview
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Brief Summary
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The study is a phase I/II trial designed to establish the safety and efficacy of intravenous administration of autologous bone marrow derived mesenchymal stem cells to patients with Parkinson's disease.

Detailed Description
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Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. A combination of genetic and environmental factors is likely to be important in producing abnormal protein aggregation within select groups of neurones, leading to cell dysfunction and then death. A large number of agents together with surgical interventions are now available to treat early and late complications of PD, but they are suffer from two main drawbacks: side effects and loss of efficacy with disease progression. Bone marrow (BM) derived mesenchymal stem cells (MSCs) an differentiate under certain circumstances into cells from various neuronal and glial type lineages; they also exert immunomodulatory effects. PD-derived MSCs are similar to normal MSCs in phenotype, morphology, and multidifferentiation capacity. Moreover, PD-derived MSCs are capable of differentiating into neurons in a specific medium with up to 30% having the characteristics of dopamine cells. These findings indicate that MSCs derived from PD patients' bone marrow may be a promising cell type for cellular therapy. BM-MSCs cultured with a cocktail of growth factors (containing FGF and BDNF) differentiate into neuronal/glial lineage cells with a predominance of cells expressing astrocytes' markers. They were effective in suppression of chronic EAE in mice and induced neuroprotection, preserving most of the axons in the CNS of successfully-treated animals. Histopathological studies revealed that MSCs could efficiently migrate into the CNS inflamed tissue (both when administered intravenously and intraventricularly) and differentiated into cells expressing neural-glial lineage markers. Such an approach may provide a feasible and practical way for PD.

Official Title
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PhaseⅠ/ⅡTrial of Autologous Bone Marrow Derived Mesenchymal Stem Cells to Patients With Parkinson's Disease.

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Biological: bone marrow derived mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with current diagnosis of idiopathic Parkinson's disease. Age 30 to 65. Experiencing motor complications despite optimized levodopa treatment. PD of Stage 2，2.5，3 or 4 of Hoehn-Yahr staging. Time between diagnosis and enrollment greater than 2 years. No significant cognitive impairment. MMSE > 24. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients may not be receiving any other investigational agents within 4 weeks of study entry. History of allergic reactions attributed to compounds of similar biologic composition to mesenchymal stem cells. Primary hematologic diseases. Patients undergo intracranial surgeries or implantation of a device for Parkinson's disease. Psychiatric, addictive or any other disorder that compromises ability to give a truly informed consent and perform all study assessments. Atypical or secondary parkinsonism. Malignancy within the last 5 years. Any other serious medical illness that might preclude safe participation in the study. Pregnant or breastfeeding women. HIV-positive patients.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC<br>Intravenous autologous bone marrow derived mesenchymal stem cells infusion to patients with Parkinson's disease. | Biological: bone marrow derived mesenchymal stem cells<br>* Intravenous administration of up to 6x10^5 MSCs per kg,qw,for 4 weeks<br>* Other names: Multipotent Mesenchymal Stromal Cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | 1 month after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect assessment | Assessed by Unified Parkinson's Disease Rating Scale (UPDRS). | 1 month after transplantation | 
| Effect assessment | Assessed by UPDRS | 3 months after transplantation | 
| Effect assessment | Assessed by UPDRS | 6 months after transplantation | 
| Effect assessment | Assessed by UPDRS | 12 months after transplantation |