Philip Van Damme and Sander Beel introduce their prolific research on brain disorders

19 November 2017
Philip Van Damme (VIB-KU Leuven Center for Brain & Disease Research) is clearly on a roll. Joined by PhD student and assistant Sander Beel, he has recently published no fewer than three pioneering research papers in the renowned academic journals Neurology, Human Molecular Genetics and Muscle and Nerve.

In your most recent paper, published in Muscle and Nerve, you describe a novel motor neuron syndrome. Can you tell us more about your findings?
Philip: “I often see patients seeking second opinions after being diagnosed with ALS. In most cases, I can confirm the diagnosis, but on some occasions, they have a different disease. In one of those incidents, the patient suffered from a disease that had never been seen before. The paper outlines the case of this patient, who had an exceptional constellation of symptoms and signs, including muscle weakness and atrophy and disturbed eye movements. An international collaboration allowed us to identify other patients with exactly the same symptoms, enabling us to describe an entirely new motor neuron syndrome. Because it could be a genetic disorder, we’re currently using next-generation sequencing techniques to look for the genes that might cause it.”

Sander, what were the biggest challenges involved in this project?
Sander: “When we first started, it took a long time to work out the model and to get used to performing microscopic surgery on mice, our model species. Even more, optimizing the conditions for the sequencing experiment was a big challenge – but luckily, we had the VIB Nucleomics core right around the corner to assist us at every step.”

And did you have any particularly memorable experiences during the research?
Sander: “Once we got the sequencing results back and identified our target, it was really motivating to see everything progress much more rapidly. We watched the pieces of the puzzle begin to fit together, which inspired us in our work.”

Philip, were there any surprises involved in the project?
Philip: “I was particularly surprised that the functions of progranulin in the lysosomes of neurons seem to be related to the neuronal growthstimulating functions.”

You divide your time between research and patients. How do you combine both aspects of your work? Do you consider it an added value to work in both spheres?
Philip: “In practice, it’s difficult to strike a good balance between research and clinical work, especially in our current medical system. However, the combination of the two is very interesting and rewarding, since the research done in both domains is often mutually enriching. One can contribute to advancements in clinical as well as in more basic research, and it enables translational research that requires the use of patient samples.”

Publications
Poesen et al., Neurology 2017
Beel et al., Human Molecular Genetics 2017
Delva et al., Muscle and Nerve 2017

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Groundwork for als diagnostic test
Amyotrophic Lateral Sclerosis, or ALS, is a scary diagnosis. With a survival rate of only 2-5 years after identification, the disease is characterized by the death of motor neurons, leading to severe muscle weakness throughout the body. Philip’s research, published in Neurology, has demonstrated that high lumbar fluid concentrations of neurofilaments, a type of motor neuron protein, is a definitive indicator of ALS. His insights could be used to develop a rapid, reliable test that accurately indicates the extent of neuron loss.

Progranulin’s new role in FTD
Sander and Philip’s paper published in Human Molecular Genetics describes a new role for progranulin, a protein that stimulates neurons to grow and heal. Patients with a genetic subtype of frontotemporal dementia show mutations in the gene that encodes progranulin, causing a loss of up to 50% of functional progranulin. The research clarifies the mechanism by which progranulin stimulates neurons, demonstrating that recovery from nerve trauma is delayed in the absence of progranulin.


Philip Van Damme and Sander Beel