Autologous Stem Cell Approach Shows Promising Early Phase 1 Data in Alzheimer Disease

At the 18th Clinical Trials on Alzheimer’s Disease (CTAD) conference, held December 1-4 in San Diego, California, investigators presented encouraging early data from a phase 1 trial evaluating Regeneration Biomedical’s direct-to-brain autologous stem cell therapy for Alzheimer disease (AD). The treatment appeared safe and well tolerated, and the program is now advancing into a phase 2 study that opened enrollment in November.¹

The early-stage study featured 9 patients, 7 of whom were included in the CTAD analysis. These participants were less than 80 years of age, had Mini Mental State Exam (MMSE) scores of 11 to 20, and exhibited elevated PET and cerebrospinal fluid (CSF) markers indicative of AD. In addition, this group had FAST stages of either 4 or 5.

Participants first underwent liposuction to obtain 50 cc of lipoaspirate, which was purified, culture-expanded, and screened to ensure that more than 50 percent of cells expressed Wnt before being cryopreserved. An Ommaya reservoir was then surgically placed subgaleally with the catheter positioned in the right frontal horn of the lateral ventricle. Using this system, patients received an intraventricular injection of the cell product—3 mL containing 2 million cells in cohort 1, 5 million in cohort 2, and 10 million in cohort 3—administered an average of 48.5 days after the initial lipoaspirate, followed by overnight observation.

Overall, treatment with the stem cell therapy was considered well tolerated, with minor adverse events (AEs) recorded during the first 2 steps of the participants’ procedures. These included minor bruising and discomfort post-liposuction and mild incisional pain after Ommaya reservoir implantation. The injection step took about 8 minutes without anesthetic and was well tolerated, with no AEs reported in any of the 7 participants up to at least 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."

On secondary, more efficacy-related outcomes, 83% of treated patients demonstrated attenuated phosphorylated tau, with a median change from 61.88 pg/ml (range, 46.9-152.75) at pre-injection to 29.75 (range, 13.20-66.55) at 12 weeks. In addition, 66% of patients had improved median amyloid PET scan centiloid score after 12 weeks, going from 137.2 (range, 53.5 to 155.5) to 100.53 (range, 55.6-168.1).

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Patients were also evaluated on Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog), a standardized cognitive assessment that measures changes in memory, language, attention, and other cognitive abilities. All told, treatment with the stem cell therapy improved scores in 83% of patients, with median values shifting from 53 (range 40 to 69) before injection to 38 (range 20 to 69) at week 12.

The FDA has cleared a phase 2 dose-ranging study (NCT07205601) to further test the efficacy and safety of the cell therapy in patients with mild to moderate AD. Approximately 115 adults will be randomly assigned 4:1 to either cell therapy RB-ADSC or placebo. Those assigned to active treatment will then be split evenly between 2 dose levels–a low dose of 2.5 x 10⁶ cells and a high dose of 5.0 x 10⁶ cells–resulting in an overall 2:2:1 randomization scheme.³

In the study, RB-ADSC will be administered intracerebroventricularly every 2 months through the implanted Ommaya reservoir over a 10-month period, for a total of up to 6 injections, followed by 6 months of post-treatment monitoring. The study’s primary and secondary objectives focus on cognitive, functional, and CSF biomarker outcomes, including phospho-tau, total tau, and Aβ42. Safety assessments, volumetric MRI using NeuroQuant, and comparative diagnostic imaging such as amyloid PET will also be conducted.

"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."

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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