Accelerating functional maturation of human ipsc-derived astrocytes
Ended Project Grant Awarded Last action
- Award ID
- R43MH135527
- Recipient
-
Brainxell, Inc. UEI CFGFE23M73T7
- Awarding agency
-
National Institute of Mental Health
National Institutes of Health, Department of Health and Human Services
- Obligated
- $275,615
Award facts
- Assistance listing
- 93.242 Mental Health Research Grants
- Completion date
- Originally
- Place of performance
- Wisconsin, USA
Award details come from USAspending.gov.
Description
- Abstract
- Neurological and psychiatric disorders, including alzheimer's disease, exert a devastating personal and economic toll on patients, families, caregivers, and society. This is in part due to our failure to develop effective medications, reflecting drug discovery platforms that are often not relevant to target diseases. The recent development of induced pluripotent stem cells (IPSCS) from humans makes IT possible to screen and validate candidate compounds on human brain cells, including those from patients, thus potentially increasing the success rate and speeding the pace of CNS drug development. Brainxell, INC. Has pioneered the development of human patient brain cell-based platforms for CNS drug discovery. Functional loss or impairment of astrocytes is implicated in a wide range of pathological processes and neural disorders, including alzheimer's disease, huntington's disease, and amyotrophic lateral sclerosis. We developed a novel method for rapid generation of enriched and functional astrocytes from IPSCS in four weeks by applying inducible expression of gliogenic transcription factors nfia and SOX9. However, ipsc- derived astrocytes are immature, comparable to those at the fetal stage, which makes IT difficult for presentation of disease phenotypes and for high-throughput screening (HTS) for drug leads intended for those whose brains are fully mature. The goal of this phase I sbir project is to uncover molecules that speed the expression of genes associated with a mature state in ipsc-derived astrocyte and to formulate cocktails that yield mature astrocyte within 1-3 weeks after plating. We will engineer a human ipsc reporter line with nanoluciferase (NLUC) fused to EAAT2 (encoded by the SLC1A2 gene), a glutamate transporter highly expressed in mature astrocytes. This line will enable and simplify the screening of small molecules for accelerating astrocyte maturation. Formulation of an effective cocktail for rapidly generating mature human astrocyte will remove a major roadblock in establishing human patient astrocyte-based HTS for CNS drug development.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $0 | |
| Original award | $275,615 |
Quick answers
Who received award R43MH135527?
R43MH135527 was awarded to Brainxell, Inc. by National Institute of Mental Health (National Institutes of Health) on August 17, 2023.
How much is award R43MH135527 worth?
$275,615 has been obligated on R43MH135527.
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