WeightControl.com: What are the main findings?
Response: In the current project we developed genetically informed repurposed medications to tackle obesity and type 2 diabetes (T2D). We can also use our platform to identify which drugs are most likely to be effective for a given individual based on their specific genetic profile.
WeightControl.com: What should readers take away from your report?
Response: There are heritable risks for obesity on T2D that provide an opportunity for precision medicine (or prevention) in different subsets of individuals with the disorders. This approach can find useful treatment from drugs that already have approval for use in other condition or drive the development of new drugs tailored to an individual’s genetic risk that relates to a particular biological component of the condition.
WeightControl.com: What recommendations do you have for future research as a result of this work?
Response: We believe this is a powerful approach that can be used for thousands of disorder and open up many new opportunities for therapeutic intervention that use personal genetic information to match people with treatments to achieve precision medicine. More specifically in relation to obesity and T2D we would like to be able to test this approach to treatment in clinical trials.
WeightControl.com: Is there anything else you would like to add? Any disclosures?
Response: We have used this approach for several other chronic disorders including respiratory disease and pneumonia (with relevance to COVID-19 associated ARDS) as well as psychotic disorders including schizophrenia and bipolar disorder.
Disclosures? To further this work we are seeking to leverage commercial investment to support the clinical trials. To achieve this we spun out the technology into a startup company called PolygenRx (https://www.polygenrx.com/).
Genetics informed precision drug repurposing for diabetes mellitus type II and obesity
S. El Shair 1 2,*, W. Reay 1 3, M. Cairns 1 3
1Precision Medicine Research Program, Hunter Medical Research Institute, 2University of
Newcastle, NSW, Australia, 3School of Biomedical Sciences and Pharmacy, University of
Newcastle, NSW, Australia
An oral presentation LBO22 at the International Congress on Obesity. The material has been extensively peer reviewed by the congress selection committee. A paper is being prepared for submission to a scientific journal but a copy is not yet available
Reay, W. R., Atkins, J. R., Carr, V. J., Green, M. J. & Cairns, M. J. Pharmacological enrichment of polygenic risk for precision medicine in complex disorders. Scientific Reports 10, 879 (2020)
Reay, W. R. et al. Genetic association and causal inference converge on hyperglycaemia as a modifiable factor to improve lung function. eLife 10, e63115 (2021)
Reay, W. R. et al. The genetic architecture of pneumonia susceptibility implicates mucin biology and a relationship with psychiatric illness. Nature Communications. 2022 Jun 29;13(1):3756.
Reay, W. R. & Cairns, M. J. Advancing the use of genome-wide association studies for drug repurposing. Nature Reviews Genetics 22, 658–671 (2021)
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