Genetic diseases are not invincible

Every day, the scientific community discovers new approaches to combat congenital diseases. A Belgian initiative is underway to develop an innovative approach that will make a major contribution to this objective.

Until recently, people with a genetic disease could do little more than try to alleviate symptoms with palliative treatments. For many people, being born with a genetic disorder is a destiny that offers little hope of effectively combating the progress of the disease.

Marfan syndrome is a rare genetic disorder. It is caused by a random mutation in the gene responsible for fibrillin production. Fibrillin is a key component of connective tissue ; it acts as a glue between cells, giving shape and strength to the body’s tissues. This mutation generally leads to too rapid skeletal growth, vision problems, respiratory problems and progressive degeneration of the heart.

Several renowned research teams are working around the world to understand why the effects of Marfan syndrome vary so much from one person to another : while some people are severely affected, others have few symptoms.

The discovery of this Holy Grail for Marfan syndrome offers a realistic prospect of improving the lives of millions of people affected by this genetic disease.

But what’s so special about this approach ?

The key to unlocking this potential is the recent breakthrough in understanding the human genome – the complex relationships between the millions of genes each individual carries, which dictate much of the behavior of each person’s body.

Researchers are now stepping up their new ability to ” see inside the genome. By combining science with powerful computer programs, they can now identify with unprecedented clarity which genetic mutations most often cause genetic disease.

Thanks to traditional genetic tools, there are already over 3,000 different mutations observed in Marfan patients. In some cases, the location and type of mutation may give some indication of the severity of the disease.

The interest of the new approach to human genomics is the potential to shed light on why an identical mutation (present, for example, in several members of the same family) does not affect individuals in the same way.

How do you counter-attack ?

New genomic tools and Big Data have made it possible to discover that some individuals do not suffer the effects of a genetic disease, even though they are carriers of a characteristic genetic mutation considered to be the cause of that disease.

These people are apparently immune. While everything indicates that they are suffering from a genetic disease, something else in their genetic heritage – i.e. in their genome – counterbalances the failure of the pathogenic gene they carry. One or more other genes modify the harmful effects of the pathogenic mutation and restore their physiological function to a normal equilibrium level. Science has coined a term for these modifier genes : ” superhero genes 

New opportunities

This discovery opened the door to a whole new world of opportunities.

It was already possible to use genetics to identify the mutation that causes a genetic disease. But while genomics is now making it possible to identify the “most important” genes, it is also possible to identify the “least important” ones. superhero genes “, which neutralize or counteract the impact of pathogenic genes, it may then be possible to use this knowledge to improve the treatment of other patients.

In the longer term, this approach could revolutionize the treatment of a large number of genetic diseases that limit the lives of hundreds of thousands, if not millions, of people in Europe and around the world.

What’s going on to get things moving ?

At the end of 2017, an innovative project got underway in Belgium to exploit the potential of this hypothesis.

The project is the brainchild of the parents of Aurélien, a two-and-a-half-year-old suffering from Marfan’s disease. Immersed in the scientific literature on this disease, they discover the potential of genomics in the treatment of genetic diseases. After numerous discussions and meetings with researchers around the world, Romain and Ludivine decided to create the ” 101 Genomes Foundation ” to support an innovative idea : the creation of a database that would combine genomic data with data on the physical condition of Marfan patients.

Once completed, the database could enable two enormous scientific breakthroughs. Firstly, it would allow us to identify the ” superhero genes ” that protect certain individuals against the negative consequences of a pathogenic mutation responsible for Marfan syndrome. Secondly, it would enable the development of new therapies to replicate the effects of the genes of ” superheroes ” and thus personalize the treatment of people with Marfan syndrome.

The idea is arousing growing interest in the scientific community specializing in Marfan syndrome. Renowned researchers from Belgium and France have formed a Scientific Committee comprising Professors Anne De Paepe, Julie De Backer, Paul Coucke, Marjolijn Renard (UZGENT), Bart Loeys and Aline Verstraeten (UZA), Guillaume Jondeau and Catherine Boileau (Hôpital Bichat) and Doctor Guillaume Smits (HUDERF).

These researchers came together to define the best strategies for establishing this data platform, and how to collect and analyze patient data. The research teams are ready to go.

Next step : raising the budget

To bring this promising and exciting idea to fruition, a challenge remains : to raise 1 million euros to set up and maintain the database over the next ten years. This budget will cover the costs of sequencing patients, as well as storing and making available the data, enabling scientists to advance their research and efforts to discover those famous genes from ” superheroes “, and consequently better target the treatment of genetic diseases.

How does this initiative serve the cause of Marfan patients ?

It is statistically estimated that one person in five thousand suffers from Marfan disease. In Belgium, around 2,000 people are affected. Around 2 million people worldwide suffer from Marfan syndrome.

In addition, the F101G database could be used to develop a methodology applicable to other genetic syndromes. The F101G could thus be seen as a pilot project with enormous potential : to improve the lives of the 700,000 rare disease patients in Belgium, 30 million in Europe, and 350 million patients worldwide.

This project is therefore a source of hope for people with Marfan syndrome, and potentially for people with other rare diseases.

In March 2018, RaDiOrg – the coupole association that brings together the bulk of Belgian rare disease patient associations – awarded F101G the Edelweiss Prize given in recognition of a unique contribution to a rare disease network.

How can you support the F101G Foundation project ?

To find out more about Marfan syndrome, visit : https: //www.marfan.org/.

For more information on F101G, please visit : f101g.org.

If you would like to make a donation and contribute to the discovery of the ” superhero genes ” that protect some people against the effects of Marfan Syndrome, you can do so via the King Baudouin Foundation. All donations are tax-deductible.

Peter O’Donnell[1] and Alisa Herrero[2]

[1]       Mr Peter O’Donell, Journalist.

[2]       Ms Alisa Herrero MSc Development Studies, Master in Political Sciences, Consultant.