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Human Microglia
Invention Summary:
Alzheimer’s Disease (AD) accounts for over 60% of dementia cases in people over 65. Individuals with Down Syndrome (DS) are at higher risk for AD and myeloid leukemia due to somatic mutations in hematopoietic cells. Interestingly, some DS individuals with AD neuropathology do not experience cognitive decline. Recent studies suggest that somatic mutations may protect against cognitive decline, though the specific mutations driving this effect remain unknown. Understanding why some DS individuals are resilient is crucial for uncovering these mutations, potentially leading to transformative cell and gene therapies.
Rutgers researchers recently identified a key mutation, CSF2RB A455D, which may contribute to cognitive resilience. Using CRISPR-Cas9 gene editing, they introduced this mutation into human pluripotent stem cell-derived microglia. The mutation, linked to DS, suppresses type-1 interferon signaling, reducing neuroinflammation and enhancing microglial functions critical for combating AD. Promising results in both in vitro cultures and in vivo mouse models suggest this approach could lead to a microglial replacement therapy for AD and other neurodegenerative diseases.
Market Applications:
- Gene therapy for Alzheimer's Disease and other neurodegenerative conditions
- Development of novel stem cell therapies for genetic diseases
- Potential for broader applications in regenerative medicine and tissue repair
- Applicable to a broad spectrum of age-related neurodegenerative diseases beyond AD
Advantages:
- Targets underlying genetic factors contributing to AD in people with DS
- Reduces neuroinflammation and enhances phagocytic & autophagic functions of microglia
- Method has shown promise in vitro & in vivo mouse models
- Offers potential for microglial replacement therapy without the need for depleting diseased microglia
Publications:
- 10.1101/2024.03.12.584646
- 10.1016/j.stem.2022.06.007
- 10.1038/s41467-020-15411-9
Intellectual Property & Development Status: Provisional application filed. Patent pending. Available for licensing and/or research collaboration. For any business development and other collaborative partnerships, contact: marketingbd@research.rutgers.edu
