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Published on: April 13, 2017
On-demand microglia deliver the therapeutic payload in Alzheimer's disease
Jessica M Thanos1, John R Lukens1
1Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, VA, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA, USA; Brain Immunology and Glia Graduate Training Program, University of Virginia, Charlottesville, VA, USA.
Abstract:
In this issue, Chadarevian et al. showed that engraftment of human iPSC-derived microglia (iMG) engineered to express secreted neprilysin (sNEP) under the plaque-responsive CD9 promoter reduces amyloid burden, neuronal damage, and inflammation in an Alzheimer's disease (AD) mouse model.1 These findings establish a cell-based strategy to treat neurological diseases.
Insights
Human induced pluripotent stem cell-derived microglia engineered to express neprilysin reduced Alzheimer's disease pathology in a mouse model. This cell-based therapy shows promise for treating neurological diseases.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Neurological Disorders
Background:
- Alzheimer's disease (AD) is characterized by amyloid plaques, neuronal damage, and neuroinflammation.
- Microglia play a crucial role in AD pathogenesis.
- Current AD therapies have limitations in addressing the complex pathology.
Purpose of the Study:
- To investigate the therapeutic potential of engineered human induced pluripotent stem cell-derived microglia (iMG) for Alzheimer's disease.
- To assess the efficacy of iMG expressing secreted neprilysin (sNEP) in reducing AD hallmarks.
Main Methods:
- Human iPSCs were differentiated into microglia (iMG).
- iMG were engineered to express secreted neprilysin (sNEP) under the control of the plaque-responsive CD9 promoter.
- Engraftment of engineered iMG was performed in an established Alzheimer's disease mouse model.
Main Results:
- Engraftment of engineered iMG significantly reduced amyloid burden in the AD mouse model.
- Treatment with engineered iMG decreased neuronal damage and neuroinflammation.
- The plaque-responsive CD9 promoter effectively controlled sNEP expression in the brain.
Conclusions:
- Engineered human iPSC-derived microglia expressing neprilysin represent a viable cell-based therapeutic strategy for Alzheimer's disease.
- This approach effectively targets key pathological features of AD, including amyloid deposition and neuroinflammation.
- These findings open new avenues for treating neurological diseases using cell-based therapies.
