Tandem 9: Identification of Disease Subtypes in Multiple Sclerosis Using Imaging / Molecular Imaging Strategies

Short Summary:

We validate multi-modal imaging techniques to develop molecular and phenotypic readouts of improved specificity allowing to reflect inflammatory and neurodegenerative processes associated with MS, thereby enable to distinguish specific MS subtypes.

Scope:

Development of molecular and phenotypic readouts of improved specificity that reflect inflammatory and neurodegenerative processes associated with MS and that will be differentially related to specific MS subtypes and animal models thereof.

Specific Aims:

The translational component of the project will focus on structural readouts such as MRI based markers of inflammation (edema, blood-brain barrier leakage, macrophage tracing, acute lesional versus chronic diffuse and likely microglia-driven aspects) and neurodegenerative processes (atrophy, deand remyelination, integrity of fiber tracts, identification of dia- and paramagnetic inclusions, cortical lesions) (Filippi et al., 2011). These readouts will be complemented by functional imaging (fMRI) to assess alterations in structural and functional connectivity in the course of the disease both in MS patients (Bonavita et al., 2011) as well as in experimental animal models. A central part of the module will be the development of target specific imaging approaches predominantly based on novel PET assays targeting specific receptors (collaboration with Prof. R.Schibli), which will complement the structural and functional readouts in stratifying the patient population. In particular, we will focus on developing imaging assays that provide specific information on MS associated pathological processes at a molecular and cellular level. This includes methods for assessing the expression/modulation of receptors related to inflammation, the infiltration of immune cells (Rausch et al., 2003), or the degree of degree of de- and remyelination (Schmierer et al., 2004). The imaging approaches will be validated in relevant animal models of the human disease and in the future also in human cell-based in vitro models. Parallel efforts that focus on genotyping, transcriptomics, proteomics and metabolic profiling in MRI-defined MS subtypes shall provide an understanding of the molecular and cellular pathogenesis of phenotypic differences. Imaging will support the development of specific disease models (e.g. transgenic mouse models), the validation of novel drug targets and to evaluation of novel therapeutic strategies.

Molecular imaging techniques used:

Magnetic Resonance Imaging, Positron Emission Tomography, Fluorescence Molecular Tomography.

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Can MS subtypes be differentiated based on a specific metabolic fingerprint / molecular imaging signature?

Added value of KFSP for this specific tandem project:

The expertise gathered in the KFSP will be beneficial for multiple tandem projects. This is particular true for markers of generic processes such as inflammation or apoptosis. Development of specific cell labeling strategies, in particular stem cells or cells of the immune system, is of interest for Tandems 1 and 3 (oncology; tumor microenvironment), Tandem 6 (atherosclerosis), Tandem 8 (mesenchymal precursor cells), Tandem 9 (stratification in MS). Similar crossfertilization across multiple projects relates to receptor-specific imaging approaches.

References