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A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
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Using human genomics to validate drug targets for acute ischemic stroke
1Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Summary
Genomic studies, like genome-wide association studies (GWASs), offer a promising approach to identify effective drug targets for acute ischemic stroke (AIS). This strategy enhances the success rate for developing new cerebroprotective treatments.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Despite extensive research into ischemic brain injury mechanisms, over 1000 drug targets have been identified, yet no cerebroprotective drugs have gained FDA approval for acute ischemic stroke (AIS).
- Traditional forward-translational research approaches have shown limited success, necessitating a shift towards reverse translational strategies.
Purpose of the Study:
- To highlight the potential of human genomics, particularly genome-wide association studies (GWASs), in validating existing drug targets and discovering novel ones for AIS.
- To explore the use of quantitative phenotypes in enabling future GWASs for studying primary and secondary ischemic brain injury mechanisms.
Main Methods:
- Review of existing research on ischemic brain injury mechanisms and drug target identification.
- Analysis of a recent genome-wide association study (GWAS) involving 6000 AIS patients, utilizing a phenotype of early neurological deterioration/improvement.
- Exploration of quantitative phenotypes, including standard of care measures, for their utility in large-scale genetic association studies.
Main Results:
- A recent GWAS identified genes associated with excitotoxicity in AIS patients, demonstrating the power of GWAS in providing human genetic support for drug targets.
- The study provides proof of principle that GWAS can identify novel targets for AIS treatment.
- Challenges remain in identifying simple, reliable, and scalable phenotypes crucial for successful GWAS in ischemic brain injury.
Conclusions:
- Human genomics, especially GWAS, significantly increases the likelihood of FDA drug approval for AIS treatments.
- Reverse translational approaches using genomics are crucial for validating drug targets and improving the success rate of cerebroprotective therapies.
- Combining genomics with other omics approaches and reperfusion therapies offers renewed optimism for effective AIS treatment.
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