Research Article: Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: A phase 1 clinical trial

Date Published: July 26, 2015

Publisher: Elsevier

Author(s): Hee Jin Kim, Sang Won Seo, Jong Wook Chang, Jung Il Lee, Chi Hun Kim, Juhee Chin, Soo Jin Choi, Hunki Kwon, Hyuk Jin Yun, Jong Min Lee, Sung Tae Kim, Yearn Seong Choe, Kyung-Han Lee, Duk L. Na.

http://doi.org/10.1016/j.trci.2015.06.007

Abstract

We conducted a phase 1 clinical trial in nine patients with mild-to-moderate Alzheimer’s disease to evaluate the safety and dose-limiting toxicity of stereotactic brain injection of human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs).

The low- (n = 3) and high-dose (n = 6) groups received a total of 3.0 × 106 cells/60 μL and 6.0 × 106 cells/60 μL, respectively, into the bilateral hippocampi and right precuneus.

No patient showed serious adverse events including fever during the 24-month follow-up period. During the 12-week follow-up period, the most common acute adverse event was wound pain from the surgical procedure (n = 9), followed by headache (n = 4), dizziness (n = 3), and postoperative delirium (n = 3). There was no dose-limiting toxicity.

Administration of hUCB-MSCs into the hippocampus and precuneus by stereotactic injection was feasible, safe, and well tolerated. Further trials are warranted to test the efficacy.

ClinicalTrial.gov identifier NCT01297218 and NCT01696591.

Partial Text

Alzheimer’s disease (AD) dementia is a neurodegenerative disease that results in progressive dementia. Currently, no approved disease-modifying treatments are available for AD. Mesenchymal stem cells (MSCs) are multipotent stem cells that are capable of self-renewal and differentiation into various cell types when cultured under appropriate conditions [1]. However, it is known that MSCs are less likely to differentiate into neurons when injected into the brain. Rather, MSCs secrete various cytotropic factors that may exert beneficial effects in AD mice through various mechanisms such as reducing amyloid burden, decreasing inflammation,or increasing endogenous neurogenesis [2], [3], [4]. Several human clinical trials have suggested that MSCs are effective in slowing down the course of neurodegenerative diseases such as Parkinson’s disease [5], multiple system atrophy [6], and amyotrophic lateral sclerosis [7], [8]. However, to the best of our knowledge, there has been no clinical trial that has attempted to treat human AD using MSCs.

This phase 1 clinical trial demonstrated that surgical stereotactic administration of a low (3.0 × 106 cells/60 μL) or high dose (6.0 × 106 cells/60 μL) of hUCB-MSCs into the hippocampus and precuneus is feasible, safe, and well tolerated in patients with mild-to-moderate AD dementia.

We conclude that stereotactic administration of hUCB-MSCs into the hippocampus and precuneus is feasible, safe, and well tolerated. We believe that our study paves the way for additional cell therapy studies. The remaining challenge is to determine if hUCB-MSC injections provide clinical benefit by either slowing or even revising the progression of AD symptoms. Further clinical trials with placebo controls, larger sample size, and a long-term follow-up period are warranted to test the efficacy of this treatment. In addition, new and effective protocols should be developed to augment the MSC effects on AD pathology and to allow repeated injections of hUCB-MSCs because the survival time of hUCB-MSCs injected in the mouse brain is reported to be approximately 4 weeks [2].Research in context1.Systematic review: The authors reviewed the literature using traditional (e.g., PubMed) sources and meeting abstracts and presentations. Preclinical studies suggest that human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs) are beneficial in Alzheimer’s disease (AD) mice. Several human clinical trials have suggested that MSCs are effective in slowing down the course of neurodegenerative diseases such as Parkinson’s disease, multiple system atrophy, and amyotrophic lateral sclerosis. However, to the best of our knowledge, there has been no clinical trial that has attempted to treat human AD by using MSCs.2.Interpretation: This phase 1 clinical trial suggests that administration of hUCB-MSCs into the hippocampus and precuneus by stereotactic injection is feasible, safe, and well tolerated.3.Future directions: Further clinical trials with placebo controls, larger sample size, and a long-term follow-up period are warranted to test the efficacy of this treatment.

 

Source:

http://doi.org/10.1016/j.trci.2015.06.007

 

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