Professor Guruprasad Aithal - From an individual to the general
From Charlotte Lee
Abstract: None of the arts theorise about individual cases’ was one of Aristotle’s rhetoric which refers to the inter-individual variation in response to a medication. Two thousand years since, fact is that vast majority of medicines work in half of those who take them. ‘Idiosyncratic’ adverse reactions remain a challenge during drug development and patient care.
Metabolism and immune system have been critical for survival of species enabling the organism to withstand starvation and infections. With an overlap of two xenophobic systems in the form of drug metabolising enzymes (evolved to deal with plant based compounds) as well as immune system (designed to respond to ‘foreign’ proteins) liver encapsulates the pre-conditions that generate ‘idiosyncratic drug-induced liver injury’.
Buoyed by the rich set of genomic information provided by the Human Genome Project and introduction of genome wide association studies, we have been able to unravel genetic basis of inter-individual variation in drug response. Capacity to induce stem cells from an individual to develop into liver cells and organoids in the laboratory will provide invaluable resource for studying biology underpinning individual’s response to drugs.
A ‘polygenic score’ that captures the risk of one developing common diseases can be estimated in a meaningful way. In precision medicine, therapies are designed and chosen on the basis of underlying biological processes, identifying those who benefit the most and protecting patients from side effects. Now reliable tests might be just around the corner.