Neural Stem Cell Therapy for Alzheimer's Disease

Neural Stem Cell Therapy for Alzheimer's Disease

Protocol Summary

| 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

| 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:

Inclusion Criteria

Exclusion Criteria

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 version
• Change from baseline to 12 months

Secondary

• Neurogenesis markers: DCX, PSA-NCAM
• Aβ42, total tau, p-tau181
• Inflammatory cytokines: IL-1β, IL-6, TNF-α

• Hippocampal volume (MRI)
• FDG-PET glucose metabolism
• Tau PET (if available)

• MMSE
• CDR
• neuropsychological composite

• 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 |
|-------|----------|
| 0 | Screening, baseline |
| 0 | Cell infusion / placebo |
| 1 | Safety assessment |
| 3 | Interim visit |
| 6 | Interim visit |
| 12 | Primary endpoint |
| 18 | Follow-up complete |

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