Project description
A novel assay will test an individual's rate of drug clearance to enable precise dosing
In 2018 alone, more than 100 new therapeutic drugs were approved in the EU and US. From over-the-counter treatments for headache to sophisticated targeted treatments requiring prescriptions, drugs must combine just the right synthesis of ingredients to combat what ails us. However, effective treatment relies equally on 'how much' as it does on 'what', and that varies from person to person based on a multitude of factors. One of the most important is how fast a drug is 'cleared' by the body. PreMeDosE is developing a nearly universal enzyme assay to test the activity level of the enzyme responsible for clearing most therapeutics. It will provide clinicians with critical information for truly personalised dosing.
Objective
PreMeDosE aims to ascertain the technical and commercial viability of a novel cytochrome P450 (CYP) enzyme activity assay, to enable truly personalised drug dosing for the first time. The CYP enzymes are responsible for the elimination of the majority of therapeutic drugs from the body. However, inter-individual variation in CYP activity leads to personal differences in drug elimination kinetics, both toxic accumulation (too slow elimination) and loss of therapeutic efficacy (too rapid elimination). The resulting adverse drug reactions have considerable clinical as well as economic consequences, accounting for ~5% of hospital admissions and increasing the mean stay from 8 to 20 days, and thereby affecting a patient’s quality of life and increasing healthcare costs. The inter-individual variation in elimination kinetics can have a genetic origin (some critical CYP enzymes are polymorphic), but substantial variations also arise from external factors, such as dietary agents, age, sex, disease state, and drug-drug interactions. Presently, only genetic variation can be measured but is not routinely recommended for clinical implementation because of the limited clinical utility. The PreMeDosE microfluidic assay permits for the first time measurement of the impacts of both genetic and external factors. The PreMeDosE assay permits direct measurement of CYP enzyme activity from a very small (biopsy-scale) liver sample, providing personalized information of drug elimination kinetics and thus paving the way to customized drug dosing. PreMeDosE assay fits standard well plate technology so it is easily implemented in routine laboratory flow. Within this project, we will optimize and validate the PreMeDosE technology with the aim to ascertain its technical and commercial viability.
Fields of science
Programme(s)
Funding Scheme
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotHost institution
00014 Helsingin Yliopisto
Finland