Early results of a "First‐in‐Human" Phase 1 clinical study of intracerebroventricular injections of ex vivo expanded, autologous, Wnt‐activated, adipose‐derived stem cells in participants with mild to moderate Alzheimer's Disease (AD)

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Vydáno v:Alzheimer's & Dementia vol. 21 (Dec 1, 2025)
Hlavní autor: Duma, Christopher M.
Další autoři: Keirstead, Hans, Nistor, Gabriel, Lynn, Robert, Buxton, Jessica J., Hareng, Zoe M, Chung, Karlyssa, Alva, Gustavo, Farmer, Sawyer H., Harris, Ashley
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John Wiley & Sons, Inc.
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024 7 |a 10.1002/alz70861_108493  |2 doi 
035 |a 3286013154 
045 0 |b d20251201 
100 1 |a Duma, Christopher M.  |u Regeneration Biomedical, Inc., Newport Beach, CA, USA 
245 1 |a Early results of a "First‐in‐Human" Phase 1 clinical study of intracerebroventricular injections of ex vivo expanded, autologous, Wnt‐activated, adipose‐derived stem cells in participants with mild to moderate Alzheimer's Disease (AD) 
260 |b John Wiley & Sons, Inc.  |c Dec 1, 2025 
513 |a Journal Article 
520 3 |a Background There is very little reported human experience with cell therapy for AD. We test the safety of using Wnt‐activated adipose tissue‐derived stem cells (ADSCs) injected directly into the ventricles of the brain to address multifactorial etiologies. Method Two million and 5 million expanded, Wnt‐expressing, ADSCs were tested in the first 5 patients ("low‐dose and medium‐dose") of a Phase 1 FDA clinical trial using escalating doses. Participants had age <80 years, FAST stages 4 and 5, and cognitive, amyloid PET centiloid scores, and CSF analyses consistent with AD. The participants underwent: 1) lipoaspiration and cell preparation, 2) Ommaya reservoir implantation, and 3) infusion of a single dose of the test product via Ommaya reservoir. The primary endpoint was safety. Secondary endpoints included normalization of phosphorylated tau (p ‐Tau), and amyloid beta, and improvement in cognitive testing scores. Result Adverse events (AEs) from pre‐injection surgical procedures included mild bruising and discomfort. Test product injection showed no AEs (range: 23‐55 weeks) including headache or nausea (Figure 1). At 12 weeks post‐injection, CSF phosphorylated tau (p ‐Tau) improved in 80% of the participants from a median of 60.2 pg/ml (range: 46.9 ‐ 76.1) to a normal median of 36.8 (range 15.0 – 66.6), amyloid PET scan centiloid scores decreased in 60% of participants from a pre‐injection median of 137.2 (range: 55.33 – 155.47) to a median of 100.53 (range: 55.58 – 168.1, Figure 3). ADAS‐cog scores improved in 80% of participants by week 12 from a pre‐injection median of 53 (range: 40 – 69) to a median of 38 (range: 20 – 69, Figure 4), MMSE scores improved in 60% of participants by week 12 from a pre‐injection median of 16 (range: 14 – 19) to a median of 18 (range: 12 – 20). Conclusion This "first‐in‐human" trial of intracerebroventricular injection of expanded autologous, Wnt‐expressing, adipose tissue‐derived stem cells proved well‐tolerated and safe for the low‐dose and medium dose cohorts. Secondary endpoints showed promising improvements. 
653 |a Stem cells 
653 |a Nausea 
653 |a Alzheimer's disease 
653 |a Body fat 
653 |a Contusions 
653 |a Brain 
653 |a Safety 
653 |a Clinical trials 
653 |a Clinical research 
653 |a Cognition 
653 |a Mini-Mental State Examination 
653 |a Humans 
653 |a Neuroimaging 
653 |a Discomfort 
653 |a Critical incidents 
653 |a Patients 
653 |a Tests 
653 |a Normalization 
653 |a Dosage 
700 1 |a Keirstead, Hans  |u Regeneration Biomedical, Inc., Newport Beach, CA, USA 
700 1 |a Nistor, Gabriel  |u Regeneration Biomedical, Inc., Newport Beach, CA, USA 
700 1 |a Lynn, Robert  |u Regeneration Biomedical, Inc., Newport Beach, CA, USA 
700 1 |a Buxton, Jessica J.  |u University of California, Berkeley, Berkeley, CA, USA 
700 1 |a Hareng, Zoe M  |u Regeneration Biomedical, Inc., NEWPORT BEACH, CA, USA 
700 1 |a Chung, Karlyssa  |u Regeneration Biomedical, Inc., Newport Beach, CA, USA 
700 1 |a Alva, Gustavo  |u ATP Clinical Research, Costa Mesa, CA, USA 
700 1 |a Farmer, Sawyer H.  |u Albany Medical College, Albany, NY, USA 
700 1 |a Harris, Ashley  |u Brain and Spine Surgeons of Orange County, Newport Beach, CA, USA 
773 0 |t Alzheimer's & Dementia  |g vol. 21 (Dec 1, 2025) 
786 0 |d ProQuest  |t Consumer Health Database 
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