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Approved research

PheWAS to support genetically-guided drug development at Eisai

Principal Investigator: Dr Adele Mitchell
Approved Research ID: 41311
Approval date: May 14th 2019

Lay summary

The primary aim of this project is to identify diseases, clinical measures, and physical traits that are associated with genetic variants that are known to increase or decrease a person's chances of developing Alzheimer's disease (AD). Specifically, we are interested in rare DNA sequence variants with measurable functional consequences within genes that are under study in Eisai's early drug development programs. By studying the effects of these variants on risk of other diseases, traits, and clinical measures, we can learn more about the function of our genes of interest. In this way, we may be able to identify potential implications of modulating the effects of those genes. For example, if a rare genetic variant that reduces a person's chances of developing AD is also found to be associated with reduced risk of Parkinson's disease, a drug that is developed to treat AD by mimicking the effect of the rare variant might also work for Parkinson's. On the other hand, if the AD risk reducing variant is associated with increased blood pressure, treating AD by mimicking the effect of the rare variant might increase blood pressure. Thus, this analysis could identify new indications or potential side effects for a drug developed to treat AD or any other disease. In addition, this type of analysis helps to characterize the function of a gene of interest and of the human variation that occurs in the gene. This information is extremely useful the drug development process and leads to a higher chance of success for a compound that reaches the clinic. Analysis of variants in genes currently under study at Eisai is projected to take three years. However, Eisai is always exploring new genes as treatment targets for AD and other diseases. Therefore, use of the UK Biobank data for this purpose will continue beyond three years. Therefore, we are requesting approval for a rolling three-year period during which we will provide annual updates. Eisai places high value on publication of research results and plans to share results from this project informally with academic and industry collaborators and formally as peer reviewed publications in scientific journals and presentations at scientific meetings.