Neural Stem Cell Therapy for Alzheimer's Disease
Protocol Summary
flowchart TD
experiments_neural_stem_cell_t["Neural Stem Cell Therapy for Alzheimers Disease"]
experiments_neural_stem_cell_t["Alzheimer"]
experiments_neural_stem_cell_t -->|"related to"| experiments_neural_stem_cell_t
style experiments_neural_stem_cell_t fill:#81c784,stroke:#333,color:#000
experiments_neural_stem_cell_t["Protocol"]
experiments_neural_stem_cell_t -->|"related to"| experiments_neural_stem_cell_t
style experiments_neural_stem_cell_t fill:#81c784,stroke:#333,color:#000
experiments_neural_stem_cell_t["Summary"]
experiments_neural_stem_cell_t -->|"related to"| experiments_neural_stem_cell_t
style experiments_neural_stem_cell_t fill:#81c784,stroke:#333,color:#000
experiments_neural_stem_cell_t["Parameter"]
experiments_neural_stem_cell_t -->|"related to"| experiments_neural_stem_cell_t
style experiments_neural_stem_cell_t fill:#81c784,stroke:#333,color:#000
style experiments_neural_stem_cell_t fill:#4fc3f7,stroke:#333,color:#000
| Parameter | Value |Study Phase | Phase IIa |Design | Randomized, double-blind, placebo-controlled |Sample Size | 60 patients (30 treatment, 30 placebo) |Duration | 12 months treatment, 6-month follow-up |Primary Endpoint | Change in ADAS-Cog13 at 12 months |Secondary Endpoints | CSF neurogenesis markers, hippocampal volume, MMSE, CDR |
Background and Rationale ...
Neural Stem Cell Therapy for Alzheimer's Disease
Protocol Summary
Mermaid diagram (expand to render)
| Parameter | Value |Study Phase | Phase IIa |Design | Randomized, double-blind, placebo-controlled |Sample Size | 60 patients (30 treatment, 30 placebo) |Duration | 12 months treatment, 6-month follow-up |Primary Endpoint | Change in ADAS-Cog13 at 12 months |Secondary Endpoints | CSF neurogenesis markers, hippocampal volume, MMSE, CDR |
Background and Rationale Adult hippocampal neurogenesis declines with age and is further impaired in Alzheimer's disease pathology. Neural stem cell (NSC) transplantation represents a novel therapeutic approach aimed at:
Direct neuronal replacement
Paracrine support via secretome
Immunomodulation to reduce neuroinflammation
Enhancement of endogenous neurogenesis
Inclusion Criteria
Age 55-80 years
Probable AD per NIA-AA criteria
MMSE score 18-26 (mild-to-moderate)
PET-confirmed amyloid positivity
Stable cholinesterase inhibitor use for ≥3 months
Caregiver available for study participation
Exclusion Criteria
Significant cerebrovascular disease (vascular dementia)
Active psychiatric disorder
History of seizures or brain surgery
Immunosuppression or active infection
Previous cell therapy participation
Intervention
Neural Stem Cell Product
Allogeneic human neural stem cells (hNSCs)
Source: fetal neural tissue (15-20 weeks gestation)
Dose: 2 × 10^7 cells in 1 mL saline
Route: bilateral intracerebroventricular infusion
Placebo
1 mL saline with 0.9% human serum albumin
Treatment Schedule
Single infusion at baseline
Immunosuppression: tacrolimus 0.05 mg/kg for 30 days
Outcome Measures
Primary
ADAS-Cog13 : Alzheimer's Disease Assessment Scale-Cognitive 13-item versionChange from baseline to 12 months
Secondary
CSF Biomarkers :Neurogenesis markers: DCX, PSA-NCAM
Aβ42, total tau, p-tau181
Inflammatory cytokines: IL-1β, IL-6, TNF-α
Neuroimaging :Hippocampal volume (MRI)
FDG-PET glucose metabolism
Tau PET (if available)
Cognitive Batteries :MMSE
CDR
neuropsychological composite
Safety :Adverse events
MRI abnormalities
Immune response to allogeneic cells
Statistical Analysis
Sample Size Calculation
Power: 80%
Alpha: 0.05 (two-tailed)
Effect size: 0.5 (ADAS-Cog13 improvement of 4 points)
20% dropout adjustment
Total: N = 60
Analysis Plan
Intent-to-treat analysis
Mixed-model repeated measures
Bonferroni correction for multiple comparisons
Timeline | Month | Activity |
Ethical Considerations
IRB approval required
Informed consent from patients and caregivers
Data safety monitoring board
Long-term follow-up registry
Expected Outcomes Based on preclinical and early clinical data, we hypothesize:
3-4 point improvement in ADAS-Cog13 vs. placebo
Stabilization or reduction in hippocampal atrophy
Reduction in CSF inflammatory markers
Good safety profile with transient immunosuppression
Risk Assessment
Risks
Intracerebral hemorrhage (rare, <2%)
Seizure (transient, <5%)
Infection from immunosuppression
Immune rejection of allogeneic cells
Mitigation
Expert neurosurgical team
Tacrolimus monitoring
Pre-treatment screening
References
Neural stem cells in Alzheimer's disease: From pathogenesis to therapy. Ageing Research Reviews (2025)
Neural stem cell transplantation for Alzheimer's disease: Progress and challenges. Stem Cell Research & Therapy (2025)
Neural stem cell therapy in Alzheimer's disease: Current clinical trial status. Alzheimer's & Dementia (2025)
Neural stem cell secretome as a therapeutic approach. Molecular Neurobiology (2024)
Show full description