Multiple Sclerosis research in vitro-to-patient toolbox

IN VITRO MODELS

Adaptive immune cells

Primary human and rodent T and B cells
Lymphocyte phenotype and function:

• Activation & Proliferation
• Suppression & Cytotixicity
• Cytokine secretion
• Migratory capacity
• Maturation/Differentiation
• Isotype class switching
• Co-stimulation & Antigen Presentation

Innate immune cells

Human and rodent monocytes and macrophages (primary cells and cell lines)
Macrophage phenotype and function:

• Phagocytosis
• Migratory potential
• Reparative and inflammatory activity

CNS resident cells

• Primary rodent glia (oligodendrocyte progenitor cells - OPCs, microglia, astrocytes)
• OPC differentiation (+ genetic and epigenetic modelling)
• Brain slices “lysolecithin induced remyelination model”
• Human and mouse blood-brain barrier models (static and flow conditions)

Techniques

Cell culture - flow cytometry - quantitative PCR - western blot - ELISA - RNA sequencing

IN VIVO MODELS

Animal models

• EAE mouse model (neuroinflammation)
• Cuprizone mouse model (acute & chronic de- and remyelination of corpus callosum)
• Lysolecithin mouse model (focal lesion model for de- and remyelination)
• Adoptive transfer & bone marrow transplantation models

Molecular read-outs

Quantitative PCR
Flow cytometry
Immunohistochemistry
Gut microbiota analysis

Functional read-outs

Disease score
Cognitive tests:

• object recognition task
• object location task
• open field task
• morris water escape maze
• spatial Y-maze
• Complex running wheel

BIOBANK

Biobank background

• Collaboration between Hasselt University, Hospital East-Limburg and Jessa Hospital
• Goal: collect, process and store high-quality biological material together with its associated clinical data
• Highest standards (following ESFRI, ECRIN guidelines)
• In total 42+ project collections (2017)
• In total 115,000+ samples (2017)

Multiple Sclerosis collections

• Plasma 1490+ samples/722 patients
• PBMC pellets 825+ samples/489 patients
• PBMC freezings 718+ samples/446 patients
• DNA 449+ samples/437 patients
• CSF 127+ samples/90 patients

Third parties can get access to the collections via a collaboration with the collecting principle investigator.

More information: www.universitybiobanklimburg.be

PATIENT STUDIES

MS network Limburg

The UHasselt Biomedical research institute and center for rehabilitation research are partnering with the Rehabilitation and MS center Overpelt and university college PXL to enable multidisciplinary and translational research to support the treatment of MS. Currently more than 700 patients are available in this network with a forecast of up to 1000 patients in the coming years.

Cross-sectional studies

• Investigate the prevalence, underlying mechanisms and relationship between frequently reported impairments and disabilities
• Optimize assessment tools to evaluate the progression of the disease, impairments and disabilities

Interventional studies

• Investigate the effect of new rehabilitation strategies such as training programs, cognitive-motor dual task training programs, exercise programs based on sonification and embodiment, task-oriented upper limb training
• Clinical pharmaceutical studies (phase 0 - 4): investigate drug therapy and the effect of therapy dosage

Techniques

• Blood analysis - muscle biopsies - gut microbiota analysis
• Movement analysis techniques - 3D movement registration using sensors
• Exercise testing and muscle dynamometry - evaluation of body composition
• Testing of functional capacity
• Evoked potentials - imaging (MRI)
• Optimization of clinical protocols and training programs
• Cognitive screenings - Questionnaires (fatigue, quality of life)
• Patient contacts - PROMs - PREMs

INVOLVED SCIENTISTS

• Prof. Niels Hellings, PhD (neuroimmunology – T cells, repair)
• Prof. Veerle Somers, PhD (immunology – B cells, biobank)
• Prof. Jerome Hendriks, PhD (immunology – myeloid cells, nutrition)
• Prof. Markus Kleinewietfeld, PhD (immunology, nutrition & microbiome)
• Dr Tim Vanmierlo, PhD (neuroimmunology – cognition)
• Prof. Bart Van Wijmeersch, MD PhD (MS neurologist)
• Prof. Veronica Popescu, MD PhD (MS neurologist, MRI specialist)
• Prof. Peter Feys, PhD (rehabilitation)
• Prof. Bert Op ‘t Eijnde, PhD (rehabilitation)
• Prof. Piet Stinissen, PhD (immunology)
• Dr Liesbet Peeters, PhD (Datascientist)

RECENT CLINICAL TRIALS

• Natalizumab observ. (NCT02677077)
• Ofatumumab Ph. 3 (NCT02792218)
• ALK8700 Ph. 3 (NCT02634307)
• Ponesimod Ph. 3 (NCT02907177)
• BAF312 Ph. 3 (NCT01665144)
• Ocrelizumab Ph. 3 (NCT03085810)
• MD1003 Ph. 3 (NCT02936037)
• Task-oriented upper limb training Ph. 2 (NCT02688231)
• Exercise + Beta-alanine supplementation (NCT03418376)
• Auditory cues and music during walking (NCT03281330)