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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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Mol Biol Rep 2019 Oct;46(5):5257-5272. Epub 2019 Jul 20.

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

Christopher Duma 1, Oleg Kopyov 2, Alex Kopyov 2, Mark Berman 3, Elliot Lander 3, Michael Elam 3, Michael Arata 3, David Weiland 4, Ruslana Cannell 5, Chad Caraway 5, Sean Berman 3, Kristin Scord 2, Lian Stemler 2, Karlyssa Chung 2, Samuel Khoudari 2, Rory McRory 2, Chace Duma 2, Sawyer Farmer 2, Anthony Bravo 2, Christian Yassa 2, Ami Sanathara 2, Elisa Singh 2, Benjamin Rapaport 2

  • 1Neurosurgery, Brain and Spine Surgeons of Orange County, Newport Beach, CA, USA. cduma@brainandspineoc.com.
  • 2Neurosurgery, Brain and Spine Surgeons of Orange County, Newport Beach, CA, USA.
  • 3Cell Surgical Network, Los Angeles, CA, USA.
  • 4School of Medicine, University of California – Irvine, Irvine, CA, USA.
  • 5Department of Neurobiology, University of California – Irvine, Irvine, CA, USA.

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 × 105 to 6.2 × 107 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.

Conclusion

We report the safety of single and repeat ICV injection of autologous fresh SVF containing progenitor stem cells in 113 injections in 31 patients followed for 3 years. ADSVF was safely injected into the human brain ventricular system over multiple injections via an implanted conduit. The secondary endpoints of clinical improvement or stability were promising in the AD and MS-P groups in particular. Complications can be minimized with prophylactic dexamethasone and the use of a VP shunt in lieu of an Ommaya reservoir. The mortality in patients with ALS and MSA appeared unaffected by the cells, but this population may need earlier intervention.

 

PMID: 31327120

To read the full article, click here doi: 10.1007/s11033-019-04983-5.

Related: ADSC; ALS; Alzheimer’s disease; Autologous stem cells; Intracerebroventricular; Multiple sclerosis; Neurodegenerative disease; Stem cells; Stromal vascular fraction.