Prize Winners

Ana BELOQUI GARCIA – UCLouvain Exploiting the pathophysiology of the gut towards innovative treatments for gastrointestinal/metabolic diseases. Rewiring of energy metabolism is a key hallmark of cancer cells. In this regard, it recently became clear that certain cancers produce high levels of serine and glycine, and that these cancers get addicted to their own serine/glycine production to sustain their excessive growth. In the first part of this work, we showed that also acute lymphoblastic leukemia belongs to the rapidly expanding group of serine/glycine synthesis addicted cancers. The second part of this study aimed at identifying clinically applicable drugs that target serine/glycine synthesis, as this is a specific vulnerability in certain cancer cells but not in healthy cells. By screening serine/glycine synthesis addicted yeast and breast cancer cell models, we identified the clinically used anti-depressant sertraline (Serlain, Zoloft) as a specific inhibitor of serine/glycine synthesis. We showed that a drug combination including sertraline efficiently impairs proliferation of serine/glycine synthesis addicted breast cancer cells in a mouse model. Our work thus supports that sertraline has the potential to be an attractive adjuvant therapeutic agent to treat the rapidly growing list of serine/glycine synthesis addicted cancers. The main limitation of current treatments relying on oral GLP-1 administration is their low and highly variable biovailability (1%). Studies in the field of metabolism exploring the physiological stimulation of GLP-1 secretion using different lipid ligands (e.g., butyrate, propionate) have failed to reach sufficiently high levels of GLP-1 in order for these to be considered as plausible treatments for metabolic disorders. We have developed a lipid-based drug delivery system (nanocapsules) that combines the physiological stimulation of endogenous gut hormone secretion (including GLP-1) with increased plasmatic levels of an encapsulated synthetic peptide. In addition, we have proven that this system does not only stimulate GLP-1, but also other gut hormones such as GLP-2, GIP or PYY. We were able to demonstrate the ability of these lipid-based nanocapsules to yield levels of the selected peptides that are therapeutically relevant in the context of different diseases, demonstrating the potential of this strategy to be used in the treatment of gastrointestinal/metabolic disorders (e.g., the so-called metabolic syndrome). This research has been conducted at the Advanced Drug Delivery and Biomaterials (Louvain Drug Research Institute) at the UCLouvain. The research has also benefited from the expertise of the research group of Prof. Patrice D. Cani (UCLouvain), the research groups of Prof. Fiona Gribble and Frank Reimann (University of Cambridge, UK) via the ERC starting grant project Nanogut and Prof. Daniel J. Drucker (University of Toronto, Canada). The nanocapsules described in this proposal are the subject of a patent (patent Lipid nanocapsules charged with incretin mimetics (PCT/EP2020/064766 24.12.2020)).

Kim De KEERSMAECKER - KU Leuven Repurposing the antidepressant sertraline to target serine/glycine synthesis addicted cancer. Rewiring of energy metabolism is a key hallmark of cancer cells. In this regard, it recently became clear that certain cancers produce high levels of serine and glycine, and that these cancers get addicted to their own serine/glycine production to sustain their excessive growth. In the first part of this work, we showed that also acute lymphoblastic leukemia belongs to the rapidly expanding group of serine/glycine synthesis addicted cancers. The second part of this study aimed at identifying clinically applicable drugs that target serine/glycine synthesis, as this is a specific vulnerability in certain cancer cells but not in healthy cells. By screening serine/glycine synthesis addicted yeast and breast cancer cell models, we identified the clinically used anti-depressant sertraline (Serlain, Zoloft) as a specific inhibitor of serine/glycine synthesis. We showed that a drug combination including sertraline efficiently impairs proliferation of serine/glycine synthesis addicted breast cancer cells in a mouse model. Our work thus supports that sertraline has the potential to be an attractive adjuvant therapeutic agent to treat the rapidly growing list of serine/glycine synthesis addicted cancers. This research has been executed at the Laboratory for Disease Mechanisms in Cancer (www.LDMC.be) at the KU Leuven and the Leuven Cancer Institute (LKI). The research has also benefited of a close collaboration with the research group of Prof. Bruno Cammue (KU Leuven) via the IOF programme of Dr. Karin Thevissen and with the research groups of Prof. Sarah-Maria Fendt (KU Leuven – VIB) and Prof. Arnout Voet (KU Leuven). The use of sertraline as an anti-cancer drug has been patented (patent Pharmacological targeting of serine/glycine synthesis (PCT/EP2019/072826 27.08.2019)).

Dr Bernard HAANSEEUW - UCLouvain Detecting Alzeimher's pathology before memory decline using new radiopharmaceuticals The lesions of Alzheimer’s disease accumulate in the brain at least a decade before memory start declining. Until recently, these lesions could only be observed after autopsy. The development of specific radio-pharmaceuticals used with PET-scans now allow visualizing Alzheimer’s lesions in the brain of normal older adults, opening new research avenues including the possibility of testing preventive therapies.

Dr Thomas VANASSCHE - KU Leuven The role of coagulates in invasive staphylococcus aureus infections Our coagulation system is a double-edged sword: it protects us against severe bleeding, but on the other hand, the majority of deaths in the western world are due to pathological activation of the coagulation system. This leads to the formation of blood clots that can cause heart attacks, strokes, and pulmonary embolisms. It becomes increasingly evident that the coagulation system is not only important to protect us against bleeding, but also plays an important role in protecting the body from infections by bacteria. But also in this case, the same paradox applies. While blood clots can ‘trap’ bacteria and prevent their spreading, some bacteria can take advantage of the coagulation system to cause more severe infections. In our work, we study how a specific bacteria, Staphylococcus aureus, uses the coagulation system to cause more severe disease. Staphylococcus aureus is one of the most frequent causes of deadly infections; more people die from infections by this bacteria than by HIV/AIDS. The number of infections by S. aureus increases every year, and even more frighteningly, the growing resistance against antibiotics makes it increasingly difficult to treat those infections. Therefore, we urgently need new therapies to be able to prevent and treat this major healthcare challenge. By better understanding how S. aureus misuses our coagulation system when it causes an infection, we can develop strategies that prevent this. In our work, we have shown that we can ‘disarm’ this dangerous bacteria by preventing its many interactions with the coagulation system. This was studied in various animal infection models, and the research continues in a clinical trial. Together with antibiotics, an approach that reduces the infectivity by preventing dangerous activation of coagulation can lead to new and more effective treatments for an important and increasing societal challenge.

Dr Philip VAN DAMME - KU Leuven Frontotemporal dementia caused by Progranulin mutations, treatable neurodegenerative disorders?

Dr Emmanuel HERMANS - UCLouvain 'Pharmacological modulation of glial glutamate uptake: manipulating the cross-talks between neuroinflammation and excitotoxicity to treat neurological disorders' In the context of degenerative or lesional diseases of the nervous system, we study the influence of inflammatory processes on the excitatory communication between neurons. Our research programs aim at developing new therapeutic approaches that would modulate inflammation originating from glial cells and affecting glutamate transmission.

Dr Eric STORKEBAUM - KU Leuven 'Role and Therapeutic Potential of VEGF in Motor Neuron Degeneration : a Study in Transgenic Mice and Rats' Amyotrophic lateral sclerosis (ALS) is a fatal motorneurodegenerative disorder that is characterized by progressive muscle weakness and wasting, ultimately leading to complete paralysis and death. We have investigated the role and therapeutic potential of the angiogenic factor VEGF in the pathogenesis of ALS. We could show that reducing VEGF levels in mice results in motor neuron degeneration, which is at least in part due to insufficient direct neuroprotective effects of VEGF on motor neurons. Furthermore, increasing VEGF levels in mouse and rat models of ALS, either by viral gene transfer or by VEGF protein administration, results in therapeutic effects in these preclinical models, with improved motor performance and increased life span.

Dr Stéphane EECKHOUDT -UCLouvain 'Contribution du CYP3A intestinal dans la métabolisation du midazolam chez le rat'

Dr Philip Van Damme - KU Leuven Frontotemporal dementia caused by Progranulin mutations, treatable neurodegenerative disorders?

Dr Marleen DEPRE - KU Leuven 'Leukotrienes'

Dr Hans DECKMYN - KU Leuven 'Contribution to the development of an effective antiplatelet drug'

Dr Yves HORSMANS - UCLouvain 'Détermination des shunts porto-systémiques chez l’homme par un test non invasif au d-propylène'

Dr Vincent LECLERCQ - UCLouvain 'Pharmacologie clinique de l’induction de l’inhibition enzymatique chez des sujets hydroxylateurs déficients'

Dr Anne HOET-VAN HECKEN - KU Leuven 'Pharmacokinetic drug interactions in man' The work ""Pharmacokinetic Drug Interactions in Man", A theoretical approach and experimental studies", reports a number of in vivo pharmacokinetic drug-drug interactions. Pharmacokinetic interactions involve changes in the processes of transport of a drug towards and removal from its site of action. Underlying mechanisms such as inhibition of oxidative biotransformation, displacement from protein and inhibition of tubular secretion are described.

Dr Jean-Pierre DESAGER - UCLouvain 'Pharmacocinétique du Fénofibrate – Contribution à l’étude de sa pharmacologie clinique'

Dr Réginald HULHOVEN - UCLouvain 'Etude pharmacocinétique de la Daunorubicine libre et complexé à l’ADN chez le lapin et en clinique humaine'

Dr Budya TJANDRAMAGA - KU Leuven 'Cardiovascular and renal effects of L-dopa : a clinical pharmacological investigation'

Dr Frank BARO - KU Leuven 'Psychopharmacological research versus treatment'