| 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
- 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
- Significant cerebrovascular disease (vascular dementia)
- Active psychiatric disorder
- History of seizures or brain surgery
- Immunosuppression or active infection
- Previous cell therapy participation
- 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
- 1 mL saline with 0.9% human serum albumin
- Single infusion at baseline
- Immunosuppression: tacrolimus 0.05 mg/kg for 30 days
- ADAS-Cog13: Alzheimer's Disease Assessment Scale-Cognitive 13-item version
- Change from baseline to 12 months
-
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
- Power: 80%
- Alpha: 0.05 (two-tailed)
- Effect size: 0.5 (ADAS-Cog13 improvement of 4 points)
- 20% dropout adjustment
- Total: N = 60
- Intent-to-treat analysis
- Mixed-model repeated measures
- Bonferroni correction for multiple comparisons
| 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 |
- IRB approval required
- Informed consent from patients and caregivers
- Data safety monitoring board
- Long-term follow-up registry
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
- Intracerebral hemorrhage (rare, <2%)
- Seizure (transient, <5%)
- Infection from immunosuppression
- Immune rejection of allogeneic cells
- Expert neurosurgical team
- Tacrolimus monitoring
- Pre-treatment screening