Autologous iNSC-DAP Cell Therapy for Parkinson's Disease (NCT05901818)

ClinicalTrials.gov Identifier: [NCT05901818](https://clinicaltrials.gov/study/NCT05901818)

Overview

The Autologous iNSC-DAP trial is a pioneering Phase 1 clinical study evaluating the safety and efficacy of induced neural stem cell-derived dopaminergic progenitor cells (iNSC-DAP) for the treatment of Parkinson's disease. This trial represents a significant advance in cell replacement therapy, utilizing the patient's own cells to avoid immune rejection concerns while providing new dopamine-producing neurons to replace those lost to neurodegeneration.

The trial is conducted by Xuanwu Hospital, Capital Medical University in Beijing, China, and is currently recruiting patients. This interventional, single-arm, open-label study aims to assess whether striatal transplantation of autologous iNSC-DAP cells can restore dopaminergic function and improve motor symptoms in Parkinson's disease patients.

Trial Details

ClinicalTrials.gov Identifier: [NCT05901818](https://clinicaltrials.gov/study/NCT05901818)

Overview

The Autologous iNSC-DAP trial is a pioneering Phase 1 clinical study evaluating the safety and efficacy of induced neural stem cell-derived dopaminergic progenitor cells (iNSC-DAP) for the treatment of Parkinson's disease. This trial represents a significant advance in cell replacement therapy, utilizing the patient's own cells to avoid immune rejection concerns while providing new dopamine-producing neurons to replace those lost to neurodegeneration.

The trial is conducted by Xuanwu Hospital, Capital Medical University in Beijing, China, and is currently recruiting patients. This interventional, single-arm, open-label study aims to assess whether striatal transplantation of autologous iNSC-DAP cells can restore dopaminergic function and improve motor symptoms in Parkinson's disease patients.

Trial Details

| Attribute | Value |
|---------------|-----------|
| NCT Number | NCT05901818 |
| Phase | Phase 1 |
| Status | Recruiting |
| Sponsor | Xuanwu Hospital, Beijing |
| Study Type | Interventional |
| Intervention | Autologous iNSC-DAP cell transplantation |
| Allocation | Single arm, open-label |
| Enrollment | 10 patients (estimated) |
| Start Date | June 13, 2023 |
| Primary Completion | December 2025 (estimated) |
| Completion Date | December 2026 (estimated) |
| Location | Beijing, China |

Background and Rationale

Parkinson's Disease and the Need for Cell Therapy

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting approximately 10 million people worldwide. The disease is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to the hallmark motor symptoms including tremor, bradykinesia, rigidity, and postural instability.

Current treatments for PD primarily focus on symptom management:

• Levodopa/carbidopa: Dopamine replacement therapy
• Dopamine agonists: Mimic dopamine effects
• MAO-B inhibitors: Reduce dopamine breakdown
• Deep brain stimulation: Surgical intervention for advanced cases

The iNSC-DAP Approach

The iNSC-DAP therapy represents a sophisticated cell replacement strategy:

This autologous approach offers several advantages:

• No risk of immune rejection
• No need for immunosuppression
• Personalized therapy
• Reduced ethical concerns compared to fetal tissue

Historical Context

Cell therapy for Parkinson's disease has a long history:

• 1980s-90s: Fetal ventral mesencephalic tissue transplantation showed promise but faced ethical and logistical challenges
• 2000s: Embryonic stem cell-derived dopamine neurons entered clinical trials
• 2010s: Induced pluripotent stem cell (iPSC) approaches emerged
• 2020s: Direct reprogramming of somatic cells (like iNSC-DAP) offers a simplified pathway

Mechanism of Action

The therapeutic mechanism of iNSC-DAP involves multiple levels of restoration:

Cellular Level

• Transplanted dopaminergic progenitors integrate into the host striatum
• Cells mature into functional dopamine-producing neurons
• Restore lost dopaminergic signaling

• New neurons extend axons to appropriate targets
• Re-establishnig nigrostriatal pathway connectivity
• synaptic integration with host neurons

Molecular Level

• Tyrosine hydroxylase (TH) expression
• Aromatic L-amino acid decarboxylase (AADC) activity
• Dopamine synthesis and release

• Secretion of brain-derived neurotrophic factor (BDNF)
• Glial cell line-derived neurotrophic factor (GDNF)
• Support host neurons

Circuit Level

• Restored inhibition of the indirect pathway
• Normalized thalamocortical motor drive
• Improved movement initiation and execution

Trial Design

Inclusion Criteria

Patients must meet all of the following criteria:

• Age 30-85 years, male or female
• Diagnosis of Parkinson's disease per MDS criteria
• Disease history over 3 years
• Hoehn and Yahr Stage ≤ 4 during "on" time
• Responsive to levodopa (≥ 30% improvement in MDS-UPDRS Part III)

Exclusion Criteria

Patients are excluded if they have:

• Atypical Parkinsonian syndrome or secondary Parkinsonian syndrome
• Other central nervous system diseases
• Severe systemic diseases or dysfunction
• Severe psychiatric disorders
• Current use of hormone or cytotoxic drugs
• Cognitive disorders (MMSE < 24)
• Severe dyskinesia (MDS-UPDRS Part 4, Item 4.1/4.2 ≥ 2)
• Previous brain surgery
• Long-term anticoagulant use
• Intracranial lesions affecting surgery or follow-up
• Inability to undergo MRI or AV133 PET
• Pregnancy or planned pregnancy

Intervention Protocol

• Peripheral blood mononuclear cell collection
• In vitro reprogramming to iNSC
• Differentiation to dopaminergic precursors
• Quality testing and expansion

• Stereotaxic navigation to striatum
• Cell implantation via precise injection
• Post-operative monitoring

• Regular assessments up to 12 months post-transplantation
• Motor function evaluations (MDS-UPDRS)
• PET imaging for cell survival
• Safety monitoring

Outcome Measures

Primary Outcomes

• Change in MDS-UPDRS Part III (motor) during "off" medication time
• Comparison to baseline values
• Time frame: Within 12 months post-transplantation

• Incidence and severity of transplant-related adverse events
• Time frame: Within 12 months post-transplantation

Secondary Outcomes

• MDS-UPDRS Part I (non-motor experiences of daily living)
• MDS-UPDRS Part II (motor experiences of daily living)
• MDS-UPDRS Part IV (motor complications)

• Purdue Pegboard test
• Gait analyzer measurements
• Daily "off" time assessment

• Unified Dyskinesia Rating Scale
• Levodopa-equivalent daily dose

• Parkinson's Disease Questionnaire (PDQ-39)
• Non-Motor Rating Scale (NMSS)

• AV133 PET imaging for dopaminergic neuron survival

Current Status and Future Directions

As of the latest update (June 2023), the trial is actively recruiting. The estimated completion date is December 2026, with primary outcome data expected by December 2025.

Potential Impact

If successful, this trial could:

• Establish iNSC-DAP as a viable Parkinson's disease therapy
• Demonstrate the safety of autologous neural stem cell therapy
• Provide proof-of-concept for personalized cell replacement approaches
• Open pathways for similar therapies in other neurodegenerative diseases

Related Approaches

Several other cell therapy approaches are in development for Parkinson's disease:

• Allogeneic iPSC-derived dopamine neurons: Japan's CiRA trial
• Mesenchymal stem cell therapy: Various Phase 1/2 trials
• Gene therapy: AAV-based approaches (AAV2-AADC, etc.)
• Exosome-based therapy: Neurotrophic factor delivery

References