Researchers at Oxford Population Health and Peking University have identified multiple potential therapeutic targets for ischaemic stroke, including six that were unknown previously. The study, published in Stroke, looked at the levels of different proteins carried in the blood.
Proteins circulating in the blood are vital for maintaining health, and their levels can provide important clues about an individual’s risk of developing certain diseases. With recent advances in technologies that enable large-scale study of proteins (proteomics), researchers can now measure thousands of proteins from small blood samples. When integrated with genetic data, these measurements can help uncover new biological insights and identify novel treatment targets for diseases such as stroke.
In this study, the researchers looked at around 2,923 proteins in blood samples from 3,977 East Asian adult participants in the China Kadoorie Biobank (CKB) study and 34,557 European adult participants in UK Biobank. They analysed this information alongside data from large genome-wide association studies (GWAS), including GIGASTROKE and a range of stroke-related risk factors including blood pressure and low-density cholesterol (LDL-C) levels.
The researchers used this data to assess whether the proteins identified could cause stroke in both the Chinese and European populations. They then looked at stroke-related risk factors and evaluated drug target information to better understand the biological functions of proteins in disease development and to identify promising candidates for new treatments.
Key findings:
- Ten proteins were found to be causally associated with ischemic stroke risk (two in East Asians, nine in Europeans), with consistent effects across both populations;
- There was strong evidence of shared genetic variants with stroke risk for nine out of ten proteins;
- Eight of these proteins were also genetically linked to major stroke risk factors, including high blood pressure, high levels of LDL-C (known as “bad” cholesterol), body mass index, type 2 diabetes, and atrial fibrillation.
- Of the ten proteins identified, three had drug targets that were already known or may be targets for existing drugs that could be repurposed (F11, ALDH2, MMP12), while six (PROCR, GRK5, FGF5, FURIN, KIAA0319, TMPRSS5) were identified as novel targets with no current therapeutic interventions.
Dr Pang Yao, Senior Molecular Epidemiologist at Oxford Population Health and lead author of the study, said ‘Our findings demonstrate the value of integrating proteomic and genomics data, across diverse populations, in biobank studies to discover novel drug targets for stroke.’
Professor Liming Li, a senior author and CKB China Principal Investigator from Peking University, said ‘Most drug targets are proteins and large biobank studies such as CKB provide a unique opportunity for undertaking cutting-edge discovery research related to drug development.’
Professor Zhengming Chen, a senior author and CKB UK Principal Investigator said ‘The results highlight the importance of proteomics for discovery of novel treatment targets for stroke. By providing supporting evidence that these proteins may cause ischemic stroke, we offer new avenues for therapeutic interventions that could have significant implications for development of precision health.’
This study demonstrates the power of large-scale biobanks that enable the study of proteins and genetics to reveal both new and repurposing drug targets for complex diseases like stroke. These targets warrant further investigation and may ultimately improve the health of global populations.