Background

This approach uses mesenchymal stem cells isolated from a patient’s own fat tissue to treat neurodegenerative diseases. The stem cells are supposed to assist in repair of damaged tissue and regeneration of cells. Compared to bone marrow stem cells, adipose stem cells are easier to obtain and are more likely to differentiate into neuron progenitors.

There is a large literature on neuroprotective and regenerative capabilities of adipose-derived mesenchymal stem cells, or exosomes derived from these cells (for review, see Pappola et al., 2024). Intravenous, intranasal, and direct brain injection of adipose-derived stem cells have been investigated in animal models of Alzheimer’s, Parkinson’s, and other diseases. In APP/PS1 AD mice, brain transplantation of stem cells activated microglia, reduced amyloid plaque load, and improved learning and memory (Ma et al., 2013). Intravenously administered stem cells were found to travel to the brain, reduce pathology, and improve learning and memory in the Tg2576 mouse model (Kim et al., 2012).

Findings

In a pilot study, a single intravenous infusion of Nature Cell Company’s Astrostem adipose-derived stem cells caused no adverse effects in spinal cord injury patients (Ra et al., 2011).

From May 2017 to August 2019, the company conducted a Phase 1/2 in 21 Alzheimer’s patients. Participants with mild to moderate AD received 10 intravenous infusions of stem cells or placebo at two-week intervals, against primary outcomes of adverse events and change in the ADAS-Cog after 30 weeks. The study ran at three locations in California and Hawaii. No results have been made public. This company registered a Phase 2 study in 100 AD patients to start in February 2023, but as of January 2025, has not started recruiting. The company is currently running a separate trial in COVID patients.

In 2017-2020, three other companies registered trials of adipose-derived stem cell preparations for Alzheimer’s, but none were conducted.

In initial work on brain delivery, investigators associated with Regeneration Biomedical injected freshly harvested, mixed adipose cell fractions into the cerebral ventricles of patients with AD, ALS, multiple sclerosis, Parkinson’s disease, or neural injury. A total of 31 patients, ranging from 41 to 83 years old,  received 113 injections and were followed for up to three years. Twelve of the injections caused one to four days of meningeal irritation, and mild temperature elevation, with two instances requiring hospitalization for symptoms. One patient had his reservoir removed and later replaced for presumed infection. The three AD patients treated had a reduction in CSF phosphoTau after injection. One AD patient, who received 12 injections over three years, showed signs of increased hippocampal volume (Duma et al., 2019).

In August 2023, the company began a Phase 1 open-label safety study of direct brain injection of purified and expanded adipose-derived stem cells in people with AD. Nine patients in three cohorts are planned to receive escalating doses of 2, 5, or 10 million autologous, adipose-derived stem cells via intraventricular injection. Participants must be younger than 80, with moderate to severe dementia, and PET and CSF evidence of AD pathology. Cells collected by liposuction are purified, and grown in culture to enrich for expression of WNT, a marker of self-renewal potential, and neuron lineage markers. The cells are delivered via a catheter into the lateral ventricle. A one-year follow-up includes repeated CSF sampling, cognitive testing, and amyloid-PET and MRI scans. Completion is expected in March 2025.

Results of the first cohort of three patients were presented at the October 2024 CTAD conference. In a poster, the company claimed only minor adverse events during liposuction and installation of the ventricle port, and no adverse events related to the infusion. In all three patients, CSF phosphoTau was lower after 12 weeks. In two patients evaluated, amyloid PET signal was also decreased. Two of the three improved on the MMSE at four or 12 weeks compared to baseline.

In other trials, additional sponsors are testing intravenous infusion of adipose-derived stem cells in Parkinson’s patients, and intrathecal injections in people with ALS.

For details on adipose-derived mesenchymal stem cell trials in dementia, see clinicaltrials.gov.