Research into rare diseases
An interview with Pierre Vanderhaeghen, Rosa Rademakers, and Ludo Van Den Bosch, three consecutive winners of the Generet Award
February 17, 2023
The Generet award, managed by the King Baudouin Foundation, is the biggest prize for rare diseases in Belgium and Europe. This year’s winner is Ludo Van Den Bosch for his research on ALS. In the previous two years, the award has gone to Pierre Vanderhaeghen and Rosa Rademakers for their work on the (mis)development of the human brain and research into frontotemporal dementia, respectively. That’s three in a row for VIB. We talked to the three neuroscientists about their passion for research, what they’ve accomplished or plan to accomplish with the one-million-euro prize, and the difficulties they face when working on rare diseases.
A passion for understanding the brain and curing rare diseases
Pierre Vanderhaeghen from the VIB-KU Leuven Center for Brain & Disease Research and ULB received the prestigious Generet prize in 2020 for his research into the development of the human brain and ways in which this goes wrong. Many rare diseases are caused by genetic mutations that make the brain develop differently, which can lead to an intellectual deficiency or autism spectrum disorder.
“You can hardly fix what you don’t understand,” Pierre explains. “Despite advances in medical and biotechnological research, there’s still much to be uncovered about rare diseases, particularly those that strike the brain, the most complex organ of all. I want to help to solve the mystery. What drives me and the team of dedicated researchers around me is our curiosity about the origins of the human brain: what makes it distinct from the brain of other species, including its sensitivity to particular diseases.”
Identifying the cause of frontotemporal dementia (FTD) has become the life’s work of Rosa Rademakers. This rare form of dementia often affects people under 65. Unlike Alzheimer’s, FTD patients do not have memory problems, but their personalities, behavior, and speech are affected. This is devastating for the patients and their families. The condition deteriorates rapidly: most patients die within ten years of diagnosis. Rosa is researching this disease while leading the VIB-UAntwerp Center for Molecular Neurology. For her work, she won the Generet award in 2021.
“I was inspired to work in the field of FTD after I came across families affected by this disease and saw the severe impact it had on their lives”, says Rosa. “I want to find the genetic factors that can cause FTD and use that information to help find a therapy for these patients.”
The newest laureate is Ludo Van Den Bosch from the VIB-KU Leuven Center for Brain & Disease Research. He wins the one-million-euro prize for his research into amyotrophic lateral sclerosis (ALS), a degenerative neurological disorder affecting motor cells. Patients usually succumb to the disease within 2 to 5 years after diagnosis. Every year, around 100,000 people die of ALS.
Ludo: “I have always been interested in understanding the underlying mechanisms of motor neuron diseases like ALS, and my research has focused on finding new ways to treat this debilitating condition.”
Research advancements
The Generet prize consists of funds that can be completely dedicated to the research plans of the three enthusiastic scientists. Since winning the prize one or two years ago, Rosa and Pierre have already made some progress in their quest.
Pierre: “Science takes time, and that’s what the Generet Fund provided us. Using their resources, we have already uncovered some mysteries about what happens in human nerve cells during their development. For example, we recently discovered a ‘cellular hourglass’ that sets the tempo of brain development, which could explain several forms of orphan neurodevelopmental diseases, which we plan to study further thanks to the Generet Fund. We plan to continue our work and make a difference for people with rare diseases.”
“The Generet award allowed us to focus on a particular group of FTD patients who develop severe changes in personality and behavior at a very young age, often in their 40s”, Rosa explains. “Through international collaborations, we are building a sample database which should allow us to identify genetic factors that contribute to this type of FTD. Identifying new genes will help us develop model systems to understand the effects of the genes and find a therapy for patients.”
Having just received his prize, Ludo plans on using the funds to continue his research in the field of ALS.
“With the Generet award’s help, I will continue my work on ALS and hope to make real progress in the field.”, says Ludo. “In previous research, we found a potential new therapeutic strategy – the inhibition of the enzyme HDAC6 – and we will focus on unraveling its mechanisms. My goal is to find new ways to treat this debilitating condition and make a difference in the lives of people affected by ALS. This will be done with my colleague Philip Van Damme, a neurologist taking care of ALS patients, and in close collaboration with the ALS Liga, the Belgian patient organization.”
Resilience in the face of rare diseases
Working on rare diseases comes with certain complexities. Obtaining funding is usually a challenge, but the Generet award provides partial relief. Each researcher mentions a distinct difficulty when asked about the obstacles they encounter, yet all ultimately express confidence in their goals.
Ludo: “The major problem is translating discoveries made in the lab into a therapeutic strategy that can be tested in the clinic, which is especially difficult for rare diseases. While we already have evidence that our strategy works in different ALS models, we need more information to understand how exactly this happens to motivate industrial partners to further develop and test this new therapeutic strategy in ALS patients. For this, the funding obtained from Generet will make a significant difference.”
“For families facing dementia, rare or common, it makes no difference. They suffer anyway. Everyone deserves help and attention,” says Rosa. “In rare, inherited diseases, the patient group is small but homogeneous. That makes it easier to conduct research and realize meaningful breakthroughs, which may also be relevant in the broader field of dementia. The main difficulty is identifying sufficient patients to allow statistically meaningful studies, but with international collaboration and the help of the Generet Award, we believe it can be done.”
“The difficulty of studying rare diseases is that they are typically very poorly known,” answers Pierre. “In many cases, everything has to be done from scratch to generate the knowledge required to understand and one day treat these conditions. This requires a lot of scientific patience and resilience, but it is also this challenge that makes our job a passion.”
About the Generet Prize
The Generet Fund, which is managed by the King Baudouin Foundation, aims to create a strong and internationally recognized research hub in relation to rare diseases in Belgium. It awards a Prize every year with a value of one million euros to a top researcher conducting research into rare diseases in Belgium. The Fund does not specify which disease(s) must be involved: all rare diseases are eligible, and any methodology that could assist research into various diseases.
Information for patients
A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via: [email protected].
