Study Overview
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Adipose_Derived_Mesenchymal_St["Adipose-Derived Mesenchymal Stem Cell Therapy fo"] -->|"references"| APOE["APOE"]
Adipose_Derived_Mesenchymal_St["Adipose-Derived Mesenchymal Stem Cell Therapy fo"] -->|"references"| GFAP["GFAP"]
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| Field | Value |
|-------|-------|
| NCT Number | [NCT06775964](https://clinicaltrials.gov/study/NCT06775964) |
| Title | Stem Cell Therapy for Early Alzheimer's Disease |
| Phase | Phase 1b/2a |
| Status | RECRUITING |
| Sponsor | Paul E Schulz, MD (UTHealth Houston) |
| Collaborator | Weston Brain Institute |
| Location | UT Health Science Center at Houston, TX |
| Enrollment | 12 subjects (estimated) |
| Start Date | February 2026 |
| Primary Completion | December 2026 |
| Study Completion | January 2027 |
Study Design
This is a Phase 1b/2a open-label, single-arm study evaluating the safety, tolerability, and efficacy of autologous, adipose-derived mesenchymal stem cells (adMSCs) in adults with late pre-symptomatic or prodromal Alzheimer's disease.
Rationale
Most currently approved AD drugs primarily treat symptoms. While anti-amyloid antibodies have successfully reduced amyloid burden, they have only modestly affected cognitive progression. This suggests that other pathological pathways are equally important for AD progression.
...Study Overview
Mermaid diagram (expand to render)
| Field | Value |
|-------|-------|
| NCT Number | [NCT06775964](https://clinicaltrials.gov/study/NCT06775964) |
| Title | Stem Cell Therapy for Early Alzheimer's Disease |
| Phase | Phase 1b/2a |
| Status | RECRUITING |
| Sponsor | Paul E Schulz, MD (UTHealth Houston) |
| Collaborator | Weston Brain Institute |
| Location | UT Health Science Center at Houston, TX |
| Enrollment | 12 subjects (estimated) |
| Start Date | February 2026 |
| Primary Completion | December 2026 |
| Study Completion | January 2027 |
Study Design
This is a Phase 1b/2a open-label, single-arm study evaluating the safety, tolerability, and efficacy of autologous, adipose-derived mesenchymal stem cells (adMSCs) in adults with late pre-symptomatic or prodromal Alzheimer's disease.
Rationale
Most currently approved AD drugs primarily treat symptoms. While anti-amyloid antibodies have successfully reduced amyloid burden, they have only modestly affected cognitive progression. This suggests that other pathological pathways are equally important for AD progression.
Neuroinflammation has emerged as a critical player in AD pathogenesis. Evidence includes:
- Elevated inflammatory markers in patients at different clinical stages of AD
- Identification of AD risk genes associated with innate immune functions
- Strong correlation between microglial activation and disease progression
This study targets neuroinflammation directly using mesenchymal stem cells, which exhibit multi-therapeutic effects:
- Anti-inflammatory properties
- Reduced amyloid-β activity
- Promotion of neurogenesis
- Low immunogenicity (autologous = patient-derived)
Intervention
Biological: adMSC — IV-infusion of autologous, adipose-derived mesenchymal stem cells (adMSCs), approximately 2×10⁸ cells in 250mL saline.
Dosing Schedule:
- 4 IV infusions over 12 weeks
- Infusions administered through a vein in the arm
Eligibility Criteria
Inclusion Criteria
Signed informed consent obtained before any study assessments
Male or female, age 60-80 years
Clinically diagnosed with late pre-symptomatic or mild cognitive impairment (MCI) due to AD (prodromal AD)
MMSE score ≥ 22
MRI to evaluate AD pathology (may use previous if within 6 months)
APOE status available (may use previous result)
Proficiency in English (cognitive tests administered in English only)
Evidence of brain amyloidosis via PET scan or Aβ42/40 ratios in CSF
Evidence of peripheral inflammatory profile based on at least one of:
- CRP ≥ 8 mg/L
- IL-6 ≥ 3.1 pg/mL
- TNF-α ≥ 10 pg/mL
- ESR ≥ 20 mm/h
10. Good general medical health per investigator assessment
Exclusion Criteria
Current neurological condition that might impact cognition (e.g., TBI, PD, MS)
Unable or unwilling to undergo neuropsychological testing
Advanced, severe, progressive, or unstable disease
History of malignancy within past 60 months
Females of childbearing potential who are pregnant
Unable or unwilling to undergo PET scans
Unable or unwilling to undergo MRI scans
Positive for HIV, Hepatitis B, Hepatitis C, or Syphilis
Positive for TSPO SNP rs6971 (affects TSPO PET tracer binding)
Unable or unwilling to undergo lumbar punctures
Unable or unwilling to undergo infusionsOutcome Measures
Primary Outcomes
| Measure | Description | Timeframe |
|---------|-------------|-----------|
| Change in TSPO levels | Measured by PET scan from baseline to midpoint and end of study | Baseline, Day 169 |
| Inflammatory cytokines in CSF | Cytokine panel measured via ELISA | Baseline, Day 169 |
TSPO (Translocator Protein) is a marker for activated microglia. TSPO PET imaging correlates with neuroinflammation levels in the brain.
Secondary Outcomes
| Measure | Description | Timeframe |
|---------|-------------|-----------|
| Treatment-related adverse events | Safety monitoring throughout study | Baseline - Day 337 |
| Neurofilament light chain (Nf-L) in CSF | Neurodegeneration biomarker | Baseline, Day 169 |
| GFAP in CSF | Astrocyte activation marker | Baseline, Day 169 |
| Total Tau/phospho-Tau ratios in CSF | AD progression markers | Baseline, Day 169 |
| FDG PET imaging | Cerebral metabolism activity | Baseline, Day 169 |
| Amyloid-β 42/40 ratio in CSF | Amyloid pathology marker | Baseline, Day 169 |
| MMSE score | Cognitive function | Baseline, Day 337 |
| RBANS scores | Neuropsychological assessment | Baseline, Day 337 |
| Lawton IADL Scale | Functional independence | Baseline, Day 337 |
| Immune pathway markers in blood | Systemic inflammation | Baseline, Day 169, Day 337 |
| Immune pathway markers in CSF | CNS inflammation | Baseline, Day 169 |
Clinical Endpoints
Cognitive Measures
- MMSE (Mini-Mental State Examination): Scoring ranges from 0-30
- 24-30: No cognitive impairment
- 18-23: Mild cognitive impairment
- 0-17: Severe cognitive impairment
- RBANS (Repeatable Battery for the Assessment of Neuropsychological Status)
- Total scores range from 40 to 160 (mean 100, SD 15)
- ≥70: Average/Mild Impairment
- 55-69: Moderate Impairment
- <54: Severe Impairment
- Lawton IADL Scale: Measures instrumental activities of daily living
- Women: 0-8 scale (8 = independent)
- Men: 0-5 scale (5 = independent)
Biomarker Endpoints
| Biomarker | Tissue | Significance |
|-----------|--------|--------------|
| TSPO | PET | Microglial activation / neuroinflammation |
| Nf-L | CSF | Axonal neurodegeneration |
| GFAP | CSF | Astrocyte activation |
| Total Tau | CSF | Neurodegeneration |
| Phospho-Tau | CSF | Tau pathology |
| Aβ42/40 | CSF | Amyloid pathology |
| FDG PET | Brain | Cerebral glucose metabolism |
Scientific Context
Neuroinflammation in AD
The brain's immune system plays a dual role in Alzheimer's disease. While initially protective, chronic neuroinflammation drives disease progression through:
- Continuous microglial activation producing pro-inflammatory cytokines
- Impaired clearance of amyloid-β and tau
- Synaptic dysfunction and neuronal loss
- Spread of pathology across brain networks
TSPO as a Biomarker
Translocator protein (TSPO, 18kDa) is expressed primarily on activated microglia and peripheral immune cells. TSPO PET imaging provides:
- In vivo measurement of microglial activation
- Quantification of neuroinflammation burden
- Potential for monitoring treatment response
Note: TSPO SNP rs6971 is an exclusion criterion because it affects tracer binding affinity, potentially confounding PET results.
Mesenchymal Stem Cells for Neurodegeneration
Adipose-derived MSCs offer several advantages:
- Autologous source: Eliminates immune rejection risk
- Multi-modal action: Anti-inflammatory, anti-amyloid, pro-neurogenic
- Low immunogenicity: Reduced GVHD risk
- Easy harvesting: Minimally invasive fat tissue collection
- Established safety profile: Demonstrated in prior clinical studies
| Role | Name | Phone | Email |
|------|------|-------|-------|
| Principal Investigator | Paul E Schulz, MD | — | — |
| Study Contact | Harshali Patel | 713-486-0531 | Harshali.Patel@uth.tmc.edu |
| Study Contact | Javier Ortiz, PhD | 713-486-0505 | Guadalupe.J.Ortiz@uth.tmc.edu |
| Study Contact | Christine Farrell, PhD | 713-486-0527 | Christine.M.Farrell@uth.tmc.edu |
Related Pages
- [Alzheimer's Disease Clinical Trials Overview](/clinical-trials/alzheimers-disease)
- [Neuroinflammation Biomarkers](/biomarkers/inflammatory-biomarkers-alzheimers)
- [TSPO PET Imaging for Neuroinflammation](/mechanisms/tspo-pet-imaging-neuroinflammation)
- [Mesenchymal Stem Cell Therapy for Parkinson's Disease](/clinical-trials/nuerownd-stem-cell)
- [GFAP as Biomarker](/biomarkers/gfap-glial-fibrillary-acidic-protein)
- [Neurofilament Light Chain](/biomarkers/neurofilament-light-chain)
- [CSF Biomarkers in Neurodegeneration](/biomarkers/csf-biomarkers-neurodegenerative-disease)
- [Amyloid-β 42/40 Ratio](/biomarkers/amyloid-beta-42-40-ratio)