Partners: TU/e, KUL, University of Luxembourg, FFUND BV, University of Sheffield, AALTO, ERASMUS MC
Novel micro-engineered in vitro models have been developed to mimic key functions of human organs. These so-called organ-on-chips (OoC) recapitulate the structure and function of human organs, and are particularly important for scientific research that is underlying our knowledge base of diseases and for the pre-clinical development of novel therapeutics. However, the application of these models has its limitations as they do not mimic the complexity and functioning of complete organ systems. Connectivity between cells and the linkage between different components of organ systems is essential in studying complex conditions such as neurodegenerative diseases. These diseases form a major challenge for the scientific community and are associated with a heavy burden on society and the global healthcare systems. To effectively grasp the complexity of neurodegenerative disorders, the CONNECT consortium develops the next level in vitro model systems for the nervous system and puts it firmly on the map. The project acts at the convergence of a multitude of disciplines including nanofabrication, microfluidics, stem cell technology, tissue engineering and advanced imaging. The successful completion of this high risk-high gain project will enable for the first time to study a complete organ system and deliver a viable paradigm for future technology to study connectivity in the nervous system. The proposed work in this project offers a unique opportunity to culture individual nervous system components and connect them in a single “smart” microfluidic chip (CONNECT platform), forming an elementary three compartment model from the central nervous system (CNS) to the peripheral nervous system (PNS). As Proof-of-Principle, CONNECT will demonstrate the feasibility of this system model in Parkinson’s Disease. This provides CONNECT with novel insights, thereby paving the way for future development of therapeutic strategies.
Partners: Leiden University Medical Center, MITOLOGICS, Janssen (Belgium), UCPH, Leiden University, FFUND BV, PRES, University of Antwerp, Medical University of Vienna
Non-tuberculous mycobacteria, such as Mycobacterium avium complex (MAC) and Mycobacterium abscessus, cause lung diseases resembling TB, mainly in immune-compromised patients or patients suffering from other lung diseases (e.g. cystic fibrosis). The incidence and prevalence of lung diseases caused by NTM are increasing worldwide. Importantly, in the US and Japan, as well as in other areas of the world where TB has declined, NTM disease is already at least three times more prevalent than TB. Treatment of NTM diseases relies on antibiotic combinations, however the drugs active against NTM are rather few and mainly different than those active against TB. These NTM treatments for the most common species (MAC and M. abscessus) are much less active than the current anti-TB regimen is for TB treatment. It is often necessary to administer antibiotic combinations for at least 12-24 months. The long and complex drug regimen that is currently recommended as a treatment against NTM-caused diseases carries the risk of inducing resistance in NTM. Several studies have already shown the existence and emergence of multidrug resistant NTM. The overall objective of RESPIRI-NTM is to find new drug candidates as potential components of a new, more efficient combination drug regimen against NTM that is less prone to resistance and allows shortening of treatment duration for NTM and multidrug-resistant NTM. Such a drug combination will synergistically target the energy metabolism of NTM or complementary targets. To achieve this, we will advance recently discovered inhibitors of the mycobacterial respiratory pathway. In addition, we will perform a novel, phenotypic screen in order to identify novel targets in NTM. Finally, we will also target host-factors that are essential for the intracellular survival of NTM. Together, we present a comprehensive plan to find novel strategies to combat non-tuberculous mycobacteria, shorten treatment time and reduce chances of drug resistance.
Partners: PRES, University of Antwerp, Leiden University, UCPH, FFUND BV, Leiden University Medical Center, MITOLOGICS, Janssen (Belgium), Medical University of Vienna
Despite recent progress in biomedical research, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is still the world’s leading infectious disease killer worldwide. In addition, multi-drug TB is the largest single contributor to anti-microbial resistance and poses a serious threat to global health. Treatment options are limited, and expensive, recommended medicines are not always available in many countries, and patients experience many adverse effects from the drugs. Moreover, due to the long treatment duration, compliance is low leading to more AMR in TB. Thus, there is an acute need for the development of a novel combination regimen with an indication for effective, shorter, and safer treatment of all forms of TB. The overall objective of RESPIRI-TB is to find new drug candidates as potential components of a new, more efficient combination drug regimen against TB that is less prone to resistance and allows shortening of treatment duration for TB, and multidrug-resistant TB. Such a drug combination will synergistically target the energy metabolism of Mtb or complementary targets. To achieve this, we will advance recently discovered inhibitors of the Mtb respiratory pathway. In addition, we will target the Mtb specific molecular mechanism that reduces reactive oxygen species in the cell. Finally, we will also target host-factors that are essential for the intracellular survival of Mtb. Together, we present a comprehensive plan to find novel strategies to combat TB, shorten treatment time and reduce chances of drug resistance.
Partners: FFUND BV, INT, UM, FUNDATIA YOUTH CANCER EUROPE, CLB, STICHTING INTEGRAAL KANKERCENTRUM NEDERLAND, ECCO, Maria Sklodowska-Curie National Research Institute of Oncology, Institut Gustave Roussy, EORTC...
STRONG-AYA is a new, interdisciplinary, multi-stakeholder European network to improve healthcare services, research and outcomes for Adolescents and Young Adults (AYA) with cancer, defined as individuals aged 15-39 years at cancer diagnosis. AYAs with cancer form a unique group; they face age-specific issues (e.g. infertility, unemployment, financial problems) and decreased quality of life due to cancer and its treatment. Unlike dedicated healthcare and trials for pediatric cancer patients, AYA-specific healthcare services are scarce and vary across Europe. AYAs who are at the core of society and economy need access to age-adjusted and high-quality healthcare. AYA-care and research will benefit from collection and pooling of patient-centered data and collaboration among all stakeholders: patients, healthcare professionals, scientists, and policymakers. Our consortium of clinical and scientific leaders in AYA-care, data science and registries, European Cancer Organisation, Youth Cancer Europe and EORTC will build on previous initiatives and EU grants. Within STRONG-AYA we will set up a value-based healthcare research ecosystem to develop data-driven, interactive policy and visualization tools that bring, in co-creation with all stakeholders including patients, novel insights into AYA healthcare. The project objectives, include: 1) Development of a Core Outcome Set (COS) for AYAs with cancer; 2) Implementation of the COS in 5 national healthcare systems (FR, IT, NL, UK, PL) and establish national infrastructures for outcome data management and clinical decision-making and a pan-European ecosystem that also welcomes future European countries; 3) Disseminate outcomes and facilitate interactions between national and pan-European stakeholders to develop data-driven analysis tools to process and present relevant outcomes, establish feedback loops for AYA cancer patients and the healthcare systems, and improve the reporting and assessment of outputs towards policy-makers.