MS is an autoimmune demyelinating disease that, in the majority of patients, evolves into a chronic neurodegenerative disease retaining an inflammatory component. As such, MS sits at the interface of immunology, inflammation and neuroscience. No single disease model adequately provides all the clinical features of MS. The world-leading expertise that Aquila has in MS research allows us to provide a unique service to understand efficacy and mode-of-action by offering novel models and assays that encompass the immunological or regenerative components of the disease, as well as expanding our service offering to provide pivotal models in MS research.
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating model commonly used as an investigative tool for the efficacy testing of new therapeutic compounds aimed at addressing debilitating human diseases such as multiple sclerosis (MS). Standard EAE models provide efficacy data, but supportive ex vivo assays are limited. Aquila’s MBP-Tracker model allows us to specifically follow the physical and functional fate of the T cells that initiate the autoimmune inflammatory lesion to provide both efficacy and mode-of action data.
To complement the MBP-Tracker EAE model, we have designed predictive moderate-throughput in vitro assays to best mimic the in vivo activation of pathogenic T cells. These allow us to study the same pathogenic T cells in vitro to obtain the best indication of the pathways targeted by test compounds, allowing more efficient progression of test compounds to in-life studies.
Remyelination of nerves occurs in MS, but it is inefficient and becomes less so as the disease progresses. Remyelination not only restores proper nerve conduction, but it also protects axons from degeneration. Improving remyelination efficiency is therefore likely to reduce disease progression in MS. For remyelination to occur, oligodendrocyte precursor cells (OPC) around lesions must survive, proliferate and differentiate into myelinating oligodendrocytes to remyelinate axons. There is considerable impetus to develop new drugs that either halt demyelination or promote remyelination to prevent damage to underlying axons. In vivo models using demyelinating toxins, administered either systemically or locally into the Central Nervous System, may be used but these only allow screening of a very limited selection of compounds as they are expensive and time-consuming studies to conduct. In vitro models have therefore been developed to study myelinating cells in culture and also the myelination efficiency of these cells in tissue slices.
Aquila BioMedical has developed a suite of in-vitro assay systems, with automated, quantitative image analyses that allow moderate throughput screening for more efficient compound selection.
Moderate throughput, high content OPC cultures can be used to asses effects of test substance on proliferation and cell death as well as more detailed Immunohistochemical analyses to assess a compound’s ability to enhance differentiation of OPCs into mature oligodendrocytes capable of myelination. Following compound screening in OPC assays, lead compounds can be progressed to slice cultures to assess remyelination efficiency in following toxin-induced demyelination. The ability of your compound to enhance remyelination is assessed using immunohistochemistry. The slice model offers a powerful screening tool for potential regenerative therapies that is both high content and moderate throughput, providing biological results in line with those which are obtained from larger and more time-consuming in vivo studies.
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