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Harnessing microglia-based cell therapies for the treatment of neurodegenerative diseases
Adeline E Walsh1, John R Lukens1
1Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia (UVA), Charlottesville, VA 22908, USA; Molecular Physiology and Biological Physics Graduate Program, UVA, Charlottesville, VA 22908, USA; Biotechnology Training Program, UVA, Charlottesville, VA 22908, USA.
Abstract:
Given the growing evidence linking microglia to the onset and progression of various neurodegenerative diseases, these brain-resident macrophages have emerged as a promising cell type for targeted therapeutic interventions. This review highlights recent studies that utilized innovative, microglia-focused strategies for the treatment of diverse neurodegenerative disorders including lysosomal storage disorders, granulin frontotemporal dementia, and Alzheimer's disease. Cutting-edge therapeutic strategies range from replacing faulty microglia with peripheral macrophage precursors or induced human pluripotent stem cell-derived microglia to engineering microglia that target toxic aggregates or deliver remediating payloads. We also examine the potential limitations as well as the clinical benefits of these strategies.
Insights
Microglia-targeted therapies show promise for neurodegenerative diseases like Alzheimer's. Innovative strategies include cell replacement and engineered microglia for treating brain disorders.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia, the brain's immune cells, are increasingly implicated in neurodegenerative disease pathogenesis.
- Targeting microglia offers a potential therapeutic avenue for conditions such as Alzheimer's disease, lysosomal storage disorders, and frontotemporal dementia.
Purpose of the Study:
- To review innovative microglia-focused therapeutic strategies for neurodegenerative disorders.
- To examine the clinical potential and limitations of these cutting-edge approaches.
Main Methods:
- Literature review of recent studies on microglia-based therapies.
- Analysis of strategies involving microglia replacement and engineering.
Main Results:
- Emerging therapies include replacing dysfunctional microglia with precursors or stem cell-derived microglia.
- Engineered microglia can target toxic protein aggregates or deliver therapeutic payloads.
- These strategies offer potential clinical benefits for various neurodegenerative conditions.
Conclusions:
- Microglia-centered therapeutic interventions represent a promising frontier in neurodegenerative disease treatment.
- Further research is needed to overcome limitations and realize the full clinical potential of these novel strategies.
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