At the recent Annual General Meeting and Conference of the Society, Professor James O’Donnell and Dr. Michelle Lavin from St. James’s Hospital, outlined the new exciting and innovative research project on haemophilia in Ireland. This new project is called the Irish Personalised Approach to the Treatment of Haemophilia (iPATH).
The research project, which will be led by Professor James O’Donnell, involves a partnership between the National Coagulation Centre in St. James’s Hospital, Our Lady’s Children’s Hospital in Crumlin, the Irish Haemophilia Society, The Royal College of Surgeons and Trinity College Dublin. It will be funded jointly by Science Foundation Ireland and by Shire.
The research project will take place over a four-year period. The objectives are to answer some fundamental questions in relation to haemophilia and to more fully understand some issues which have an impact on treatment and care. The project aims to develop a greater understanding of the biology underlying haemophilia. There are fundamental questions to which we still do not have answers. If you take a group of people with severe haemophilia, despite the fact that they all have factor levels of less than one percent, some of the individuals will bleed far more frequently than others. Why is it that some patients get more spontaneous bleeds than others, despite having the same low factor level in their blood?
Similarly, if you look at several boys with severe haemophilia who have had a similar number of bleeds into a joint over a period of time, some will develop much more serious joint damage than others. Others will have well-preserved joints, despite lots of bleeds into that joint. We do not understand the biological difference which causes this. Ireland has a number of advantages when it comes to carrying out research projects such as this. We have a small homogenous population. People with haemophilia are all registered at the National Coagulation Centre (NCC) and attend one of the small number centres regularly. We have extremely good and relatively complete data on the use of factor concentrates and bleeding rates from the home treatment app on people’s smartphones. Consequently, we have a lot of information about the clinical impact of haemophilia in each individual.
Part of the project will involve doing a full genome analysis of every person with severe or moderate haemophilia who signs up to take part in the research project. Interestingly, in the United States, a full genome analysis has been carried out on some five thousand people with haemophilia. However, the US does not have the same level of information about bleeding rates and factor use.
By looking at treatment records and joint assessments, the research project can identify groups of individuals who bleed less often than others with severe haemophilia and can identify groups of individuals who have less joint damage, despite having a significant number of bleeds into particular joints. They can then look for specific genetic sequences in the genome of those individuals and hopefully may identify genetic sequences which are linked to preventing bleeding or helping to prevent joint damage. This, in turn, may lead the project in the direction of developing biomarkers or tests which can be used to reliably stratify bleeding risk and/or the risk of developing joint damage in people with haemophilia.
It is also highly probable that some of the differences in bleeding rates and in the developing of joint arthropathy are due to the variations in individual immune responses. This research project could conceivably identify those differences and develop targeted immuno-modulated therapies which could assist in optimally protecting joints against joint damage. The research project will also allow the development of knowledge of individual pharmacokinetic profiles of each person with severe haemophilia.
The half-life of factor VIII (FVIII) which averages at approximately 12 hours, varies from 6 hours to 29 hours in particular individuals. The impact of this variation in the half-life of the individual can be identified during the course of this research project. Once we have a greater understanding of the biological basis underlying the variation in bleeding and joint damage in people with severe haemophilia, we can more clearly design optimal personalised treatment regimens for each person, in addition to potentially developing adjunctive therapies, which can help to prevent joint damage or specific biomarker assays, which can help to identify variations in bleeding patterns. The I.H.S. are delighted to be involved as a partner in this very exciting innovative research project.
The National Coagulation Centre is already well known internationally for research work on von Willebrand’s Disease. We believe that this research project will now place the haemophilia community in Ireland at the very forefront of global research in relation to haemophilia. It should provide a significant amount of valuable information which will assist the clinicians here in optimally treating people with haemophilia in the future and may help to answer these fundamental questions in relation to bleeding patterns and joint damage, which will be of benefit to people with haemophilia globally.