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Cited by 85Mesenchymal stem cell researchMultiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration Mechanisms

Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients

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Duma, Christopher, Kopyov, Oleg, Kopyov, Alex, Berman, Mark, Lander, Elliot, Elam, Michael, Arata, Michael, Weiland, David +15 more·2019·Molecular Biology Reports
DOI 10.1007/s11033-019-04983-5
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Abstract

We have chosen to test the safety of human intracerebroventricular (ICV) brain injections of autologous non-genetically-modified adipose-derived stromal vascular fraction (ADSVF). In this IRB-approved trial, 24 patients received ICV ADSVF via an implanted reservoir between 5/22/14 and 5/22/17. Seven others were injected via their ventriculo-peritoneal shunts. Ten patients had Alzheimer’s disease (AD), 6 had amyotrophic lateral sclerosis (ALS), 6 had progressive multiple sclerosis (MS-P), 6 had Parkinson’s “Plus” (PD+), 1 had spinal cord injury, 1 had traumatic brain injury, and 1 had stroke. Median age was 74 (range 41–83). Injections were planned every 2–3 months. Thirty-one patients had 113 injections. Patients received SVF injection volumes of 3.5–20 cc (median:4 cc) containing 4.05 × 10 5 to 6.2 × 10 7 cells/cc, which contained an average of 8% hematopoietic and 7.5% adipose stem cells. Follow-up ranged from 0 to 36 months (median: 9.2 months). MRIs post injection(s) were unchanged, except for one AD patient whose hippocampal volume increased from < 5th percentile to 48th percentile (NeuroQuant ® volumetric MRI). Of the 10 AD patients, 8 were stable or improved in tests of cognition. Two showed improvement in P-tau and ß-amyloid levels. Of the 6 MS-P patients all are stable or improved. Four of 6 ALS patients died of disease progression. Twelve of 111 injections (11%) led to 1-4 days of transient meningismus, and mild temperature elevation, which resolved with acetaminophen and/or dexamethasone. Two (1.8% of injections) required hospitalization for these symptoms. One patient (0.9% of injections) had his reservoir removed and later replaced for presumed infection. In this Phase 1 safety trial, ADSVF was safely injected into the human brain ventricular system in patients with no other treatment options. Secondary endpoints of clinical improvement or stability were particularly promising in the AD and MS-P groups. These results will be submitted for a Phase 2 FDA-approved trial.

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  • Compared to IT route, ICV administration accesses the ventricles requiring an invasive stereotaxic surgery but has been demonstrated to be safe in clinical trials and achieve widespread AAV distribution in the brain.

    “Comparing to IT route, ICV administration accesses the ventricles requiring an invasive stereotaxic surgery but has been demonstrated to be safe in clinical trials and achieve widespread AAV distribution in the brain [93].”

    From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [93]

    The Ommaya reservoir implantation technique describes image-guided surgery to place a ventricular catheter, and the Safety section reports on ICV injections in a phase 1 trial. But the trial administered ADSVF cells, not AAV, and the paper does not demonstrate widespread AAV distribution in the brain. It also notes that patients with an existing VP shunt did not require reservoir implantation. (LLM, conf=0.90)

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Authors
Duma, C., Kopyov, O., Kopyov, A., Berman, M., Lander, E., Elam, M., Arata, M., Weiland, D., Cannell, R., Caraway, C., Berman, S., Scord, K., Stemler, L., Chung, K., Khoudari, S., McRory, R., Duma, C., Farmer, S., Bravo, A., Yassa, C., Sanathara, A., Singh, E., & Rapaport, B.
Affiliations
University of California, Irvine (US)
Corresponding author
  • Duma, Christopher
  • Duma, Chace
ORCID
Venue
Molecular Biology Reports
Publisher
Springer Science and Business Media LLC
Published
2019-07-20
Volume
46
Issue
5
Pages
5257-5272
ISSN
  • 0301-4851 (ISSN-L)
  • 1573-4978
DOI
10.1007/s11033-019-04983-5
OpenAlex
W2962677494
Cited by
85
References
124
Citations by year
2026: 5 · 2025: 10 · 2024: 17 · 2023: 12 · 2022: 13 · 2021: 18 · 2020: 8 · 2019: 1 · 2018: 1
FWCI
5.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Biology Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
intracerebroventricular administration, stromal vascular fraction, autologous cell therapy, neurodegenerative diseases, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, ventriculoperitoneal shunt, safety, cognitive function, hippocampal volume, meningismus
MeSH terms
Adipose Tissue, Adult, Aged, Aged, 80 and over, Female, Hematopoietic Stem Cells, Humans, Male, Middle Aged, Transplantation, Autologous, Treatment Outcome, Ventriculoperitoneal Shunt, Hematopoietic Stem Cell Transplantation, Neurodegenerative Diseases, Mesenchymal Stem Cell Transplantation, Infusions, Intraventricular

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