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The personalised medicine

A new research project will be studying the genetic basis of why individuals with the same diagnosis respond differently to the same medicine. The research results can contribute to personalised medicine in the future, based on our unique genetic profile. Medicine with more effect and less side effects.

2018.11.23 | Jette Odgaard Villemoes

Graphical representation of the three contributing mechanisms assumed to cause drug response variability. Mechanism 1: A set of disease associated genetic variants are decisive for the risk of developing the disease, and the response to drug treatment varies among cases as a consequence of genetic variation in genes in e.g. drug metabolic pathways. Consequently, the rate and amount at which the body absorbs drugs varies among cases leading to variation in drug response, hence, the disease and drug response phenotypes are effectively two traits that genetically are uncoupled. Mechanism 2: The drug response variability is a consequence of variability in the disease per se, i.e. there are disease heterogeneity among the cases, which results in differences in response to treatment. The disease heterogeneity is not a result of genetic variation among the cases, but due to different lifestyle choices, different environmental exposures, and different genetic risks for correlated diseases. Mechanism 3: Heterogeneity in the associated genetic variants that causes the same disease results in variation in how individuals respond to the same medical treatment.

 

People with the same diagnosis often react differently to the medicine they are prescribed. Some will not have the maximum benefit of the effect of the medicine; others may experience too many side effects. A best-case scenario for patients as well as doctors would be the possibility to target medicine individually to each patient in order to gain maximum effect and minimum side effects.

A core issue in the attempt to get closer to a general implementation of personalised medicine is the understanding of the mechanisms behind the fact that patients with the same diagnosis respond differently to the same medicine. Because there are both genetic and environmental factors involved. The current knowledge about the genetic background is too limited, and this is why further research is necessary.

Project manager Palle Duun Rohde from the Center for Quantitative Genetics and Genomics (QGG) at the Department for Molecular Biology and Genetics, Aarhus University in Foulum, who received a three-year grant from the Lundbeck Foundation, elaborates:

”There are probably many different causes to why patients with the same diagnosis respond differently to the same drug treatment, but we suggest three mechanisms, which we can actually test statistically: First, the disease and the patient’s reaction to the treatment are two independent events, caused by different genetic markers. Second, that patients with the same diagnosis have lived their life differently, and that differences of lifestyle and environmental impacts trigger subcategories of the disease, and thereby also the treatment as such. Third, that even though the patients have different, genetic profiles which all lead to the same disease, it is the unique combination of a patient’s total, genetic risk that contribute to the patient’s reaction to the drug treatment.”

The project will be carried out in close collaboration with the Big Data Institute at the University of Oxford and the director of the Institute, professor Gil McVean. The Institute  has an extensive databank at their disposal, with large, complex and heterogeneous dataset for research in diseases. The objective is to develop a new analytic tool that can clarify the genetic background for the reason why patients with the same diagnosis respond differently to the same medicine treatment. The disease categories to be examined are metabolic diseases, categories of cancer and mental diseases.

Palle Duun Rohde, whose PhD thesis studied the genetic understanding of schizophrenia and ADHD, is happy with the unique opportunity to get closer to an individual and targeted, medicinal treatment of patients:

”I am immensely happy and proud that the Lundbeck Foundation has given me the opportunity to contribute with knowledge which in time – hopefully – can help patients. It is incredibly exciting to work on an understanding of the underlying, genetic mechanisms for human diseases, and I believe my work with schizophrenia and ADHD during my PhD has given me a solid foundation for taking a step further towards a better understanding of the genetic causes of variable responses to treatment. I am very much looking forward to beginning my project, and hopefully it will also contribute to even more focus on human diseases at QGG.”

As for the future prospects of a general implementation of individually adapted medicine if the project succeeds in developing a new, analytic tool, he says:

”It is obvious that there is a long way from the work, I will be doing, to an actual implementation of personalised medicine treatment. But that does not make my work less interesting or less relevant. For the majority of diseases we simply do not have the necessary knowledge to be able to use genetic profiles to choose the best treatment. That is why there is a need for plenty of new knowledge, for instance how we can use large amounts of data in the best possible way. My hope is that this project can contribute with knowledge and strategies to how we can exploit genetic data in combination with other types of data, for instance lifestyle and environmental impact, in the best possible way. I believe that in the future genetic profiles will have a decisive influence in the treatment of many diseases – we just need to figure out how to use these data.”

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Project title: Untangling the Genetic Basis of Drug Response.

Period: 26 February 2019 – 25 February 2022

For more information: Postdoc Palle Duun Rohde, Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University. palle.d.rohde@mbg.au.dk

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