Pharmacogenetics is a field of research that looks at how a patient’s genes affect their responsiveness to medication. This new study, led by Dr Trinidad Montero-Melendez from the William Harvey Research Institute at Queen Mary University of London, will investigate how genetic variations in a gene called melanocortin 1 receptor, MC1R, affects the anti-arthritic property of a novel drug called AP1189, developed by SynAct Pharma, which is under clinical investigation for the treatment of rheumatoid arthritis. The results from this study are expected to provide rationale for a personalised medicine approach, consisting of giving the right drug to the right patient.
The treatment of many chronic inflammatory diseases like rheumatoid arthritis are based on trial-and-error algorithms, in which patients are sequentially prescribed different medications until one that is effective is found. This, not only delays the improvement of the disease but also leaves patients suffering unnecessarily from the side effects from medications that do not work. Therefore, understanding in advance which mediations will be effective for each patient will allow an informed medical decision rather than a trial-and-error approach, undoubtedly resulting in patient benefit.
Dr Montero-Melendez commented: "Many drug targets show genetic variation in the human population that may result in altered drug response. This project will investigate the impact of genetic variants on the efficacy of novel therapy for rheumatoid arthritis and other chronic inflammatory diseases aiming to provide rationale for personalized medicine”. This translational project builds on a previous long-term collaboration with SynAct Pharma during which we discovered the innovative ‘biased agonist’ mode of action of the drug [1] and contributed to its pre-clinical development, results that were published in The Journal of Immunology.
“In addition to the benefits of Pharmacogenetics in clinical practice, the integration of this strategy into the drug development process also has the potential to accelerate the development of novel medicines”, commented Professor Mauro Perretti, co-investigator of the project. In fact, by taking the genetic variations of drug targets and their impact on efficacy into account during the design of a clinical trial, researchers have the potential to improve success rates and accelerate the adoption of these new therapies.
“The project is a natural next step in our long-standing collaboration with Dr Trini-Montero Melendez and Professor Mauro Perretti. Our investment of ~£400,000 is to enable an important task of the project, i.e. to link clinical outcome of treatment with our biased melanocortin agonist AP1189 in RA patients to melanocortin type 1 receptor polymorphism as it would give the possibility to apply a personalized medicine approach for future clinical studies. In addition, new insight into pharmacology of specific melanocortin type 1 variants can be used for identification of next generation compounds”, commented CSO, Thomas Jonassen, SynAct Pharma AB (publ).
[1] Montero-Melendez T et al. Biased agonism as a novel strategy to harness the pro-resolving properties of melanocortin receptors without eliciting melanogenic effects. The Journal of Immunology. 2015;194(7):3381-8.