The central nervous system and neuroprotection as weapons in the fight against multiple sclerosis

Interview with Prof. Vincent VAN PESCH, Clinical Director at the Cliniques universitaires Saint-Luc, Head of the Neurochemistry Unit of the Cellular and Molecular Division, Institute Of NeuroScience (IONS), UCLouvain

What is the prevalence of multiple sclerosis in Belgium and what do we know about the causes of this pathology? Multiple sclerosis (MS) is one of the most common neurological diseases in young adults (aged 20 to 40 years): MS affects 14,000 people, two-thirds of whom are women, and 450 to 500 new cases are diagnosed every year in Belgium, of which about 50 by the Cliniques universitaires Saint-Luc. This multifactorial disease involves genetic susceptibility but also environmental factors such as lack of solar exposure, which results in vitamin D deficiency, the effects of certain viral infections (especially the Epstein-Barr virus), environmental pollution and lifestyle (smoking, overweightness in children).

Could you please present your research work on multiple sclerosis to us? As a neurologist, my team monitors a pool of more than 1,000 patients. Our centre has participated in numerous clinical trials to test new innovative molecules that have reached the market in recent years. Today, over 15 phase II, III and IV trials are in progress. I also participate in the international register of MS, MSBase, which is actively involved in studies on the epidemiology of the disease and the indirect comparison of MS treatments. As a clinical biology consultant who is also responsible for the neuroimmunological analysis protocols, I also conduct translational research by introducing new diagnostic tests (implementation of quantitative assaying of free Kappa chains in cerebrospinal fluid).

My fundamental research work focuses primarily on the characterisation of immunological biomarkers in relation to the activity

of the disease in order to understand the immune disturbances correlated with inflammatory relapses of the disease versus its remission phases. I’m also working on microRNAs, which are small molecules produced by cells that are involved in autoimmune diseases, in order to characterise their expression in association with the relapse and remission phases of the disease. The study of the cerebrospinal fluid, blood and immune cells in the patients allowed us to establish the fact that the disease originates in the central nervous system. We identified a panel of microRNAs that allowed us to distinguish patients from unaffected individuals and - within the group of patients - those who are in the active phase of the disease. Using in vitro cell models, we still need to study the origin and functions of the microRNAs in order to understand their role in immune physiopathology and demyelination. Finally, as part of a collaboration with Prof. Van Snick and Dr Uyttenhove of the Ludwig Institute for Cancer Research at UCLouvain, we tested a mouse monoclonal antibody that neutralises GM-CSF, a highly inflammatory molecule, and demonstrated that preventive treatment using this antibody prevents the development of the disease in mice. © UCLouvain

What research projects are you currently working on? Current projects in the area of translational research involve cognitive follow-up of MS patients and the development of new brain imaging biomarkers. As regards clinical trials, phase III pharmacological trials will begin in 2020 and certain phase IV trials are looking at the medium- and long-term effects of new medicines on the real-life treatment of MS patients different from the hyper-selected patients of the phase III trials. In addition, together with Prof. des Rieux, an expert in nanomedicines, and Prof. Muccioli, an expert in bioactive lipids at the Louvain Drug Research Institute, I have established a consortium for the study of bioactive components of extracellular vesicles in MS and the development of nanomedicines capable of better penetrating the central nervous system.

In your opinion, what are the main challenges awaiting multiple sclerosis? The key challenges are to be able to directly target the central nervous system and to develop neuroprotective or even neuroregenerative approaches in addition to the current immunological approach. Stimulating damage repair already appears to be the new frontier for researchers, who want to stabilise the disease while at the same time looking for ways to improve the functional prognosis of patients.