"A unique and unprecedented example of patient participation in scientific research" by Prof. Anne De Paepe

2018 /Thursday, October 18th, 2018

Rare genetic diseases, such as Marfan syndrome, have long been a neglected area of medicine. Because of their rarity, the knowledge and interest of the medical profession is often insufficient, so that many patients go through a long period of research to obtain an accurate diagnosis, follow-up and possible treatment. Because of the small number of patients, pharmaceutical companies are generally reluctant to invest in research that can lead to better treatments.

The increased attention given to rare diseases by the scientific and medical community and, more recently, by national and European policy-makers, is mainly due to patient associations who have understood that they need to themselves to make their own case. Significant advances in scientific knowledge and renewed interest in these rare diseases are therefore largely due to the initiatives taken by patients and their families. They have worked hard to improve communication and knowledge about rare diseases and to launch large-scale fundraising initiatives to raise the financial resources needed to support research. In this regard, the associations of patients of Marfan syndrome are exemplary, with the ABSM in Belgium among others, and the French and American marfan associations that have been working for years with dedication and efficiency to support scientists and clinicians involved.

Patients with Marfan syndrome are at increased risk of serious cardiovascular complications resulting in premature death. Although life expectancy has improved considerably in recent years thanks to more accurate and faster diagnostic methods and the possibility of preventive aorta surgery, there is currently no adequate drug available for prevent, treat or cure serious complications of the disease, let alone prevent it. Great progress has been made in diagnosing and determining responsible genetic dysfunction: it is a mutation of the gene encoding fibrilline 1, an important protein for the formation of connective tissues that support the wall aortic, among others. Today, many fibrillin 1 mutations are known and molecular research into the diagnostic establishment of a suspected case of Marfan syndrome has become almost standard. But the discovery of the gene responsible and its alterations did not explain the great variability in the severity of clinical manifestations, according to which patients, even those with the same fibrilline mutation 1, same family as in different families - have considerable differences in the nature and severity of clinical symptoms, complications and life expectancy. Why does one patient have life-threatening aortic dilation and another has mild prolapse in the heart valve? Why does one patient suffer from serious eye problems and only one from mild myopia? And why are skeletal abnormalities so variable? Are certain hereditary and/or environmental factors protective and other aggravating factors?

The extraordinary evolution we are currently experiencing in the field of genetic technology (including whole genome sequencing) and bioinformatics offers unprecedented perspectives for discovering new strategies for research that can lead to an answer to these questions.

Romain and Ludivine Alderweireldt, parents of Aurelien, who has Marfan syndrome, understood this very well. Driven by an exceptional motivation and willingness to make a "10-year" leap forward in scientific research on Marfan syndrome and thus offer their son - and with him the entire Marfan community - a better perspective of the future, they are are familiar with the scientific, legal and ethical aspects of scientific research with astonishing speed and efficiency and have created, with the support of the King Baudouin Foundation, their Fondation 101 Génomes to raise the necessary financial resources (fundraising).

With the 101 Marfan Genomes project, they aim to provide a bioinformatics platform that will contain very accurate clinical and genomic data on a cohort of 101 Marfan patients whose clinical profile and severity of symptoms vary. This platform will be, on request motivated, searchable and usable by all researchers involved around the world. By cross-referencing the phenotypic and genomic databases, they hope to identify the "modifying genes" that determine clinical variability, eventually exert a "protective" or "aggravating" effect and could thus lead to the discovery new drugs or treatments that could prevent serious complications.

The project is stimulating and very ambitious and, as with any innovative and original research, the result is not predictable. It is certain that it will lead to new discoveries that will be useful not only for Marfan syndrome, but also for many other genetic diseases.

There are also several strong assets that strengthen the project's chances of success: for its implementation, Romain and Ludivine have assembled a multidisciplinary team of high-level clinical and genetic experts on Marfan syndrome in Belgium and Paris, as well as experts in molecular biology and bioinformatics. They also surround each other with valuable legal and ethical skills. The research strategy chosen is unique, based on preliminary results that are already interesting and uses the latest and most effective techniques to analyze the entire genome. In addition, special attention will be paid to the recording of specific clinical data, which is one of the most difficult and sensitive aspects and therefore often the weak link of this type of research initiative. Finally, thanks to the established relationships, this project will be able to be aligned with important European initiatives, such as the European Reference Network (ERN) and will be brought to the attention of large international consortiums around Marfan syndrome and aortic aneurysms such as the MAC consortium (Montalcino Aortic Consortium).

The enthusiasm and motivation of Romain and Ludivine make the 101 Genomes project a unique and unprecedented example of patient participation in scientific research. It is a fantastic model and a source of inspiration for many other rare diseases! They deserve our full support, respect and admiration!


Anne De Paepe
Chair of the Fonds 101 Génomes King Baudouin Foundation
Professor of Human Genetics and Proctor of the University of Ghent

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