Prof. Dr. Pierre Vanderhaeghen from VIB-KU Leuven has been awarded the Generet Prize for Rare Diseases for his research on human brain development. Vanderhaegen’s team have developed an astonishing model for studying rare neurological disorders by successfully integrating human neurons into a mouse brain. The prestigious prize, managed by the King Baudouin Foundation and presented to Vanderhaeghen by HRH Princess Astrid, includes EUR 1 million in funding for further studies.
By Amy LeBlanc
Despite millennia of fascination with the human brain, scientist still struggle to study the complex organ. One of the most challenging aspects of neuroscience is studying the brain in vivo; working with cells in the laboratory is extremely limiting, as we need to observe the complex interplay between different cell types to get a clear picture of how things work. Or, in the case of many rare diseases, how things aren’t working as they should during brain development.
Human neurons in a mouse brain
Prof. Pierre Vanderhaeghen has been fascinated by brains ever since his youth, when his father (a neuroscientist), brought one home to dissect together in the kitchen. Nowadays, Vanderhaeghen is an internationally renowned neuroscientist himself, in charge of a lab at the VIB-KU Leuven Center for Brain Research and teaching at KU Leuven and ULB, his alma mater.
“You can only fix what you understand,” says Vanderhaeghen, explaining the motivation behind his research. “There is still a lot we do not know about rare diseases, which can often cause severe disabilities. I want to help to solve the mystery. What drives me and the team of amazing researchers around me most of all is our curiosity about what is going on in our heads.”
You can only fix what you understand. There is still a lot we do not know about rare diseases… I want to help to solve the mystery. – Pierre Vanderhaeghen
To aid research into neurological disorders, Vanderhaeghen and his team have developed a breakthrough mouse/human chimera model. The team injected human neurons generated from stem cells into the visual cortex of neonatal mice. As the mouse brains developed, the human neurons formed connections with their murine neurons, integrating into the cortex in a functionally meaningful way: tests showed that the human neurons would respond to visual stimuli like basic black and white pattern.
Read this previous BioVox news piece to learn about human neurons in mouse brains advancing Alzheimer’s research.
The success of the chimeric model means that we are now able to study neuronal development in the living brain. “We can now look at the cellular and molecular level,” says Vanderhaeghen. “You don’t have that resolution with a brain scan like a CT. This chimera model could be a powerful tool for studying a range of disorders that affect neuronal development. What’s more, the fact that these neurons are able to functionally integrate into the cortex has interesting and exciting implications for the prospect of brain repair therapies.”
Human brain cells are slow to develop
Many rare neurological diseases are caused by genetic mutations that result in errors in brain development. These can translate into learning disabilities, epilepsy, loss of motor functions and other serious issues. “We suspect that in a lot of these diseases, the error is in the pace of neuronal development: they are developing either too slowly or too quickly,” Vanderhaeghen explains. “One remarkable feature of human neurons is their prolonged development. It takes years for some of them to develop to maturity, while it only takes a few weeks in mice and a few months in non-human primates. This slow development is thought to be at the origin of many higher cognitive features of our species, because it allows young humans extended periods of plasticity and learning.”
Our model can be used for research into countless rare disorders, but science takes time. – Pierre Vanderhaeghen
When Vanderhaeghen’s team used the new chimeric human/mouse model to study the speed of neuronal development, they found that the human neurons still showed a much slower maturation than the mouse neurons. This finding is important, because it shows that human brain cells have their own internal clock mechanism, yet to be discovered, that directs the pace of neuronal maturation. Finding out how this works could be a game changer for rare brain diseases caused by developmental issues.
Understanding rare diseases
Together with a spin-off that specializes in repurposing existing drugs for the treatment of rare diseases Vanderhaeghen and his team have already begun research into the rare conditions MECP2 duplication and RETT syndrome. Both are rare genetic neurodevelopmental disorders that lead to severe impairments, affecting nearly every aspect of the child’s life: their ability to speak, walk, eat, and even breathe easily. Using the new model, Vanderhaeghen can transplant cells from the patient, containing all the genetic information, into the mouse brain. This allows the researchers to study the development of the disease and gain a better understanding of what is going wrong.
Read this previous BioVox article to learn about another Belgian breakthrough in rare genetic diseases.
Reflecting on the prestigious Generet Prize, Vanderhaeghen concludes: “Our model can be used for research into countless rare disorders, but science takes time. We are very happy to have the resources provided by the Generet Fund, since they give us the time and freedom to try things out. In the next two to four years we will definitely be making a lot of discoveries about what happens in human nerve cells during their development. That first step is vital to allow us to make a difference later on for people with rare diseases.”
Header Image: Prof. Dr. Pierre Vanderhaegen © Laboratory of Stem Cell and Developmental Neurobiology (VIB-KU Leuven Center for Brain Research)
