Mesenchymal Stem Cells With Adjuvant Dexamethasone in Patients With Alzheimer’s Disease: A Phase IIa Trial

Background and Purpose: This phase IIa trial assessed the safety and efficacy of mesenchymal stem cell (MSC) therapy for Alzheimer's disease (AD). An open-label extension (OLE) further explored the adjunctive role of dexamethasone. Methods: MSCs (n=24) or a saline placebo (n=12) were administered intraventricularly three times at four-week intervals. In the OLE, MSCs and dexamethasone (15 mg, n=5) were administered to patients who received saline in phase IIa. Clinical parameters and cerebrospinal fluid (CSF) markers were evaluated. Results: MSC therapy exhibited no significant clinical benefits, but was associated with reductions in CSF AD biomarkers (amyloid-beta, phosphorylated-tau, and total-tau) compared to placebo. The MSC group experienced more adverse events (fever, headache, nausea, and vomiting), while co-administration of dexamethasone appeared to attenuate immune-related reactions and limit increases in CSF white blood cell and interleukin-6. Conclusions: These findings suggest exploratory biological effects of MSCs on AD biomarkers, with dexamethasone potentially mitigating MSC-induced immune responses. Trial Registration: ClinicalTrials.gov Identifier: NCT02054208, NCT03172117, and NCT04954534.