Autologous Stem Cell Therapy for Alzheimer Disease Advances to Phase 2 After Positive Early Findings

A version of this story originally appeared on our sister site, NeurologyLive.

At the 18th Clinical Trials on Alzheimer’s Disease (CTAD) conference, held December 1-4, 2025, in San Diego, California, investigators shared promising phase 1 data supporting the safety and feasibility of RB-ADSC, an autologous Wnt-enriched stem cell therapy delivered directly to the brain for patients with Alzheimer disease (AD).^1,2

Developed by Regeneration Biomedical (RBI), the therapy leverages intracerebroventricular administration via an Ommaya reservoir to target ventricular stem cell niches. Following positive early results, the program has progressed to a phase 2 clinical trial, which began enrolling patients in November 2025.

Seven patients were included in the CTAD analysis out of 9 total in the dose-escalation phase 1 study. Participants were under 80 years old, had Mini-Mental State Examination (MMSE) scores between 11 and 20, and demonstrated evidence of AD through elevated PET and cerebrospinal fluid (CSF) biomarkers. All were categorized as FAST stage 4 or 5.²

Treatment involved harvesting 50 cc of lipoaspirate via liposuction, followed by purification, expansion, and selection for Wnt expression. Cells were cryopreserved until administration. A subgaleal Ommaya reservoir was surgically implanted, with the catheter placed in the right lateral ventricle. Intraventricular delivery of the cell product (3 mL) occurred a mean of 48.5 days later: 2 million cells for cohort 1, 5 million for cohort 2, and 10 million for cohort 3. Patients were observed overnight post-injection.

The approach was generally well tolerated, with minor adverse events (AEs) including localized discomfort from liposuction and mild incision pain following reservoir placement. Notably, no AEs were reported following the intracerebroventricular injection, even up to 25 weeks post-procedure.

"We are honored to share our phase 1 findings at CTAD," Christopher Duma, MD, FACS, founder of RBI and inventor of the direct-to-brain delivery method, said in a statement.¹ "Our therapy uses autologous stem cells enriched for Wnt expression, with the goal of stimulating dormant ventricular stem cell populations. The feasibility, safety, and early cognitive signals observed in this first-in-human study underscore the urgent need for regenerative strategies."

Preliminary efficacy signals were also encouraging. Investigators reported that 83% of treated patients demonstrated reductions in CSF phosphorylated tau, with a median drop from 61.88 pg/mL (range, 46.9–152.75) at baseline to 29.75 pg/mL (range, 13.20–66.55) at 12 weeks. Additionally, 66% of participants experienced improvements in amyloid PET centiloid scores, with a median shift from 137.2 to 100.53 over the same period.

On the cognitive front, 83% of patients exhibited improved scores on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog), with median scores decreasing from 53 (range, 40–69) at baseline to 38 (range, 20–69) at week 12.

Based on these findings, the FDA has cleared a phase 2 randomized, double-blind, placebo-controlled trial (NCT07205601) to assess safety, dosing, and clinical efficacy in a larger population of approximately 115 adults with mild-to-moderate AD.³ Participants will be randomized 4:1 to receive RB-ADSC or placebo, with those on active therapy further stratified into low (2.5 x 10⁶ cells) and high (5.0 x 10⁶ cells) dose cohorts. The therapy will be administered intracerebroventricularly every 2 months via the implanted Ommaya device, for up to 6 total doses across 10 months, followed by 6 months of observation.

Primary and secondary endpoints include cognitive and functional outcomes, alongside CSF biomarker changes (p-tau, t-tau, Aβ42), volumetric MRI (via NeuroQuant), and amyloid PET imaging. Safety assessments are ongoing.

"With this FDA clearance, RBI advances into Phase 2 and continues its mission to develop a regenerative therapeutic that may restore, not just preserve, neural function,” Bill Miller, chief executive officer at Regeneration, said in a statement.¹ "We are actively seeking strategic investment from family offices, institutional partners, and individuals committed to changing the trajectory of Alzheimer disease."

REFERENCES
1. RBI, Inc. to Present their Phase 1 First-in-Human, Direct-to-Brain Autologous Stem Cell Therapy Results at CTAD 2025. News release. December 1, 2025. Accessed December 3, 2025. https://fox59.com/business/press-releases/ein-presswire/871494470/rbi-inc-to-present-their-phase-1-first-in-human-direct-to-brain-autologous-stem-cell-therapy-results-at-ctad-2025/
2. Duma C, Keirstead H, Nistor G, et al. Results of a "First-in-Human" Phase 1 Clinical Study of lntracerebroventricular Injections of Ex Vivo Expanded, Autologous, Wnt­-Activated, Adipose-Derived Stem Cells in 6 Participants with Mild to Moderate Alzheimer's Disease (AD). Presented at: 2025 CTAD Conference; December 1-4; San Diego, CA. Abstract P079
3. Study of Intracerebroventricular Injections of Autologous Adipose-Derived Stem Cells (RB-ADSCs) in Participants With Mild-Moderate Alzheimer's Disease. Clinicaltrials.gov. Updated October 3, 2025. Accessed December 3, 2025. https://clinicaltrials.gov/study/NCT07205601