Ageing and Chronic diseases

Bruxelles Woluwe

Cystic fibrosis is a genetic disease leading to the production of viscous mucus, notably in the respiratory tract, which favors chronic colonization by specific bacterial species, causing life-threatening infections. The group of Françoise Van Bambeke (cellular and molecular pharmacology; TFAR) is studying the mechanisms leading to resistance and to tolerance to antibiotics in this specific patients’ population, with a specific interest for resistance by efflux and for tolerance related to the formation of biofilms or to the intracellular survival of bacteria.

Oral delivery of biologics and poorly water soluble drugs is hindered by both the physicochemical properties of the drug molecule and physiological barriers in the gastrointestinal tract. Therefore, to overcome these limitations, Prof V. Préat, Dr A. Beloqui and their team are exploring and optimizing nanomedicines as a promising drug delivery systems with applications in high-impact diseases such as inflammatory bowel disease, type 2 diabetes mellitus, and obesity. Nanoparticles can improve the oral bioavailability of both hydrophobic and hydrophilic drugs, as well as biologicals via different mechanisms: enhancing the solubility, prevention against premature degradation in the intestine, enhancing intestinal permeation and targeted drug delivery.

Profs. N. Delzenne, P. Cani and L. Bindels are co-leading collaborative and interdisciplinary research projects dedicated to unrave the mechanisms linking the gut microbiota and host metabolism in several pathological contexts.

Using innovative technologies, they investigate the role of specific bacteria (e.g. Akkermansia, Lactobacillus, Faecalibacterium, Bifidobacterium species), gut peptides, bacterial metabolites and gut-microbiota-targeting foods and drugs in several metabolic disorders.

Our ultimate goal is to offer a better understanding of the crosstalk between gut microbes and their host in physiological and pathophysiological contexts, in order to pinpoint new therapeutic targets and tools for the treatment of metabolic diseases through the modulation of the gut microbiota.

Obesity, metabolic disorders and cardiovascular diseases have reached epidemic proportions over the last decade and new innovative tools, both at the preventive and therapeutic levels, are warranted. The gut microbiota plays a key role in energy homeostasis and metabolic regulation. By combining preclinical and clinical studies, Profs. N. Delzenne, P. Cani and their teams are dedicating their efforts to the evaluation of the interest and role of the gut microbiota as a therapeutic target to tackle obesity, metabolic syndrome, and cardiovascular disease. Current clinical studies such as Microbes4U and Food4Gut will help answering the key question of the relevance of innovative tools targeting the gut microbiota in obesity.

Inhalation aerosols offer a targeted drug therapy for chronic respiratory diseases such as asthma. However, the rapid elimination of therapeutic proteins from the lungs implies the requirement to deliver them once daily and this imposes a significant therapy burden to patients. Prof. R. Vanbever investigates the potential of PEGylation for sustaining the presence of therapeutic proteins in the lungs. Her team has demonstrated that the covalent attachment of a large polyethylene glycol chain to therapeutic proteins greatly prolongs their presence in the lungs. This prolonged pulmonary residency translates into an improved efficacy in reducing lung inflammation in murine models of asthma.

A large number of chronic diseases affecting the central nervous system or the periphery are either driven or accompanied by chronic inflammation. Typical examples are multiple sclerosis, obesity, or inflammatory bowel diseases. Strong evidence supports an important role for bioactive lipids in the physiopathological processes at play in chronic diseases. Thus, at the BPBL research group we use targeted and untargeted lipidomic approaches to characterize how lipid mediators are altered in these diseases and the effect of these lipid mediators on disease progression. The aim of these studies is to propose new therapeutic perspectives based on the modulation of the endogenous levels of bioactive lipids.

The therapeutic potential of novel potent drug that address diseases of the central nervous system is often limited by a low bioavailability, off target toxicity and limited access of therapeutic molecules to the CNS (blood-brain-barrier). One strategy developed by Prof A. des Rieux and her team to address these limitations is to develop new drug delivery systems (nanomedicines) that would specifically deliver drugs to the CNS. Drug encapsulation in nanoparticles would protect the drug, increase its solubility and its transport across biological barriers. These systems are currently tested in models of multiple sclerosis and spinal cord injury but could be used for other pathologies.

Regenerative medicine aims at restoring organ function that was lost due to a pathology or an accident. Most of the strategies that are being explored involve stem cells. Limiting factors are cell survival after injection, cell engraftment, potential formation of tumors and host rejection. Combination of biomaterials and drug delivery is one of the approaches that Prof. A. des Rieux and her team use to address these issues. We are currently exploring the potential of dental stem cells for spinal cord injury and inflammatory diseases and developing different strategies to deliver them in the central nervous system.

Cardiovascular diseases (CVD) remain the main cause of death in Europe and, overall, CVD are estimated to cost the European Union (EU) almost €200 billion a year. Of this, more than €100 billion is due to health care costs, with drug expenses accounting for 29%. Belgium is not an exception where CVD medication costs reach approximately €900,000 per year. The causes of CVD are multifactorial and directly related to elevated blood cholesterol and triglyceride levels. HMG-CoA reductase inhibitors or statins are the most widely prescribed drugs in this context. Today, it is estimated that about half of the population over 50 is taking statin. Atorvastatin is the world’s bestselling drug of all time. However, despite this clinical success, and although doses are titrated according to cholesterol measurements, many individuals are unable to reach their respective targeted levels defined by the Systemic COronary Risk Estimation (SCORE). In addition, many patients suffer from side effects, and up to 10% of patients taking atorvastatin experienced muscle-related adverse drug reactions. Thus, there is a pressing need to identify biomarkers that might allow a better control of cholesterol levels through statin medication with an optimal safety and comfort for the patient. By bringing together complementary expertises, we provide here a unique multidisciplinary approach that will integrate all aspects of biomedical sciences necessary to push statin therapy a big step further. The ambition is to develop a new horizon in population PK (Laure Elens) with the support of colleagues in analytical chemistry (Prof G.G. Muccioli), pharmacogenomics (Prof V Haufroid) and clinical medicine (Prof JL Balligand).