Research team

Bio-Imaging lab

Screening platform for peripheral neuropathies in induced pluripotent stem cell derived 2D and 3D models. 01/01/2022 - 31/12/2022

Abstract

Charcot-Marie-Tooth (CMT) neuropathies are progressive peripheral neuropathies resulting in muscle weakness and atrophy. The development of efficient therapies is complicated by the tremendous clinical and genetic heterogeneity of these incurable hereditary neuropathies. Most CMT therapeutic studies are in a laboratory or pre-clinical phase, and only one phase III clinical study was reached for the most common form CMT type 1A. So far, all therapeutic studies have been performed in specific small animal models mimicking one specific gene mutation causing a CMT disease subtype. It is only theoretically possible to create an animal model for every gene mutation that causes CMT (more than a thousand mutations), and it involves high cost and ethical objections (3R principle for the use of laboratory animals). In addition, since the disease symptoms typically only appear in (young) adulthood, complications that can arise during the development of transgenic laboratory animals and a long lead time must be taken in consideration. Moreover, the metabolism between humans and small laboratory animals differs significantly, which can have implications for determining the correct dose and the long-term effects of a drug. The iPSC technology offers a solution for this. We have recently been able to demonstrate that induced pluripotent stem cell (iPSC)-derived nerve cells from CMT type 2 patients, caused by different gene mutations, share common features. We also showed that we could partially restore progressive mitochondrial dysfunction in these iPSC neurons by means of a therapeutic molecule. The test platform developed by us consists so far of: - Measuring nerve outgrowth; - Determining the axonal transport; - Characterizing the mitochondrial dysfunction; - Phenotyping by means of microscopic techniques. SCREEN4PN aims to further optimize, build and standardize the platform, and most importantly, extend it from a 2D to a 3D cell model by introducing neuromuscular organoids (NMOs). The goal is to offer this 2D and 3D platform to the pharmaceutical industry, clinical research organizations (CROs), and academic institutions. Initially, SCREEN4PN will be a testing platform for CMT-targeted therapies, but this will be extended to other peripheral neuropathies and neuromuscular disorders. The iPSC testing platform (2D and 3D), SCREEN4PN, should significantly shorten the process for testing drug candidates and biomarkers for this diverse group of hereditary neuropathies; by a factor of 5 compared to animal research (from more than a year to 4 months). The cost of screening candidate therapeutic molecules should also be reduced by a factor of 4. The number of experiments and the experimental variability, inherent to animal research, should also reduce. The SCREEN4PN platform, consisting of patient and control-derived iPSC neurons and NMOs (2D and 3D cultures), combined with standardized assays, will benefit the pharmaceutical industry in evaluating and/or validating their therapies or biomarkers in a relevant model; not only for CMT but also for other related neuromuscular and neurodegenerative disorders. The ultimate intention is to offer this niche CRO activity to the pharmaceutical industry, CROs and academia through a Spin In or Spin Off.

Researcher(s)

Research team(s)

IMARK. Network for image-based biomarker discovery and evaluation 01/01/2021 - 31/12/2026

Abstract

IMARK capitalizes on the deeply rooted expertise in biomedical imaging at the University of Antwerp to push the boundaries of precision medicine. By resolving molecular and structural patterns in space and time, IMARK aims at expediting biomarker discovery and development. To this end, it unites research groups with complementary knowledge and tools that cover all aspects of imaging-centred fundamental research, preclinical validation and clinical evaluation. IMARK harbours high-end infrastructure for electron and light microscopy, mass spectrometry imaging, magnetic resonance imaging, computed tomography, positron emission tomography and single-photon emission computed tomography. Moreover, IMARK members actively develop correlative approaches that involve multiple imaging modalities to enrich information content, and conceive dedicated image analysis pipelines to obtain robust, quantitative readouts. This unique blend of technologies places IMARK in an excellent position as preferential partner for public-private collaborations and offers strategic advantage for expanding the flourishing IP portfolio. The major application fields of the consortium are neuroscience and oncology. With partners from the Antwerp University Hospital and University Psychiatric Centre Duffel, there is direct access to patient data/samples and potential for translational studies.

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Biomedical Microscopic Imaging and in-vivo Bio-Imaging (EGAMI). 01/01/2015 - 31/12/2020

Abstract

EGAMI stands for Expert Group Antwerp Molecular Imaging. Moreover, EGAMI is the mirror word of 'image'. EGAMI clusters the internationally recognized expertise in the profession of fundamental and biomedical imaging at the University of Antwerp: the Bio-Imaging Lab, the Molecular Imaging Center Antwerp (MICA), Radiology, the Laboratory for Cell Biology and Histology, and the Vision Lab (for post-processing of medical images). EGAMI's mission is providing an integrated research platform that comprises all aspects of multimodality translational medical imaging. Multimodality refers to the integration of information from the various imaging techniques. Within EGAMI, there is pre-clinical and clinical expertise and infrastructure for magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). EGAMI executes projects ranging from applied biomedical (imaging) and fundamental research to imaging methodologies. Die applied biomedical research focusses on the research fields neuro(bio)logy (i.e. development and validation of biomarkers (as well as therapy evaluation) for diseases like Alzheimer's, schizophrenia, multiple sclerosis etc.) and oncology (i.e. biomarkers for improved patient stratification and therapy monitoring). Since the pre-clinical biomedical research within EGAMI makes use of miniaturized versions of imaging equipment for humans (scanners) is it inherently translational, in other words initial findings acquired in animal experiments can be translated into clinical applications for improved diagnosis and treatment of patients ('from bench to bedside'). Beside the application of imaging in the biomedical research, EGAMI also conducts projects that aim to achieve an improvement and optimization of the imaging methodology. The expertise of the MICA (e.g. the development of new radiotracers) and of the Vision Lab (e.g. the development of image reconstruction, segmentation, and analysis algorithms) offers here the strategic platform to assemble intellectual property rights.

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Research team(s)