Regeneration Biomedical has reported encouraging interim results from its first-in-human Phase 1 clinical trial evaluating Wnt-activated, autologous, adipose-derived stem cells (RB-ADSCs) injected directly into the brain for treating mild-to-moderate Alzheimer's disease. The data, which will be presented at the International Society for Cell & Gene Therapy meeting in New Orleans, shows promising cognitive improvements and biomarker changes in the first five patients treated.
Significant Cognitive and Biomarker Improvements
The trial demonstrated notable clinical benefits across multiple measures. Eighty percent of patients showed improvements in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores, with median scores improving from 53 pre-injection to 38 post-treatment. Additionally, 60% of patients showed improvements in Mini-Mental Status Examination (MMSE) scores, with median scores increasing from 16 to 18.
Biomarker analysis revealed substantial reductions in disease-associated proteins. Eighty percent of patients showed decreased p-tau levels, with median concentrations dropping from 60.2 pg/ml pre-injection to 36.8 pg/ml post-treatment. Amyloid PET imaging also demonstrated improvements, with median centiloid scores decreasing from 137.2 to 100.53.
Favorable Safety Profile
The treatment demonstrated a strong safety profile with no immediate or delayed major adverse effects reported across the 23 to 55-week follow-up period. This represents a significant finding for a therapy involving direct brain injection, as noted by principal investigator Gustavo Alva, M.D., who stated that "regenerative therapies like RB-ADSCs may offer a superior safety profile and a more comprehensive approach with meaningful benefits for patients living with this devastating disease."
Novel Direct Brain Delivery Approach
The RB-ADSC therapy employs an innovative delivery method that bypasses the blood-brain barrier by injecting stem cells directly into the brain's lateral ventricles. The treatment uses highly purified, Wnt-activated adipose-derived stem cells obtained from patients' own adipose tissue. Following collection, the stem cells are cultured and expanded in vitro, selected for Wnt expression, and reintroduced via an Ommaya reservoir implanted under the scalp.
Trial Design and Future Plans
The ongoing open-label, single-arm study is enrolling nine patients with mild-to-moderate Alzheimer's disease using a 3+3 single-dose escalation design. The primary objective is to assess safety and determine a recommended dose for a potential Phase 2 trial. Secondary endpoints include Alzheimer's disease clinical assessments along with biochemical and anatomical biomarkers, with each participant followed for up to 12 months post-treatment.
Christopher Duma, M.D., President and Founder of Regeneration Biomedical, indicated the company is "actively exploring next steps, including a Phase 2 trial and see potential opportunities to investigate this approach in other neurodegenerative diseases in the future, pending further data and regulatory guidance."
Addressing Unmet Medical Need
The results come at a time when current Alzheimer's treatments primarily target amyloid plaques while leaving other critical disease mechanisms unaddressed. As Dr. Alva noted, "AD remains one of the greatest unmet medical challenges, with current treatment options primarily targeting amyloid plaques, while leaving other critical issues unaddressed."
The therapy is designed to stimulate the activation and maintenance of stem cells in regenerative regions of the brain while reducing inflammation, addressing key factors in neurodegenerative diseases through a regenerative approach rather than solely targeting protein aggregates.
