ProMyelo GmbH is a highly specialized preclinical research organization offering services that focus on the development of new neural therapies, especially in the field of Multiple Sclerosis research. ProMyelo’s various preclinical MS model Systems (cuprizone, EAE, LPC etc.) and applications (immunohistochemistry, ultrastructural analyses, gene expression studies, cell culture approaches, etc.) provide high-quality standard and customizable solutions for basic science, preclinical and clinical research. We provide these specialized research services to pharmaceutical & biotechnology companies, non-profit organizations and academic researchers.
EAE is the model most commonly used to study efficacy of potential drugs for treatment of multiple sclerosis (MS).
Because of its many similarities to MS, EAE is used to study pathogenesis of autoimmunity, CNS inflammation, demyelination, cell trafficking and tolerance induction. EAE is characterized by paralysis (in some models the paralysis is remitting-relapsing), CNS inflammation and demyelination. EAE is mediated by myelin-specific CD4+ T cells, but CD8+ cells and B cells may also play a role in some models of EAE.
In principal, EAE can be induced in two ways:
By immunizing animals with myelin-derived proteins or peptides (active EAE) or by injecting animals with CD4+ T cells specific for myelin-derived peptides (adoptive or passive EAE).
Protecting demyelinated axons is critical to maintain neural integrity as transection/loss of axons is the major cause of neurological decline in MS patients. The extent of axonal damage can be studied in various animal models.
Axonal transection or loss is a notable pathology in MS as a consequence of demyelination of axons in the brain. Protecting demyelinated axons is critical to maintain neural integrity as transection/loss of axons is the major cause of neurological decline in MS patients. ProMyelo’s mouse models can evaluate neuroprotection potential
of pharmaceutical compounds and biologics by analyzing the swollen and transected axons that are reminiscent of neuronal damage. In addition, ProMyelo’s electron microscopy capabilities allow comprehensive analysis of the neuroprotective effect by studying neuronal ultrastructural changes.
Experimental End Points
Characteristic for Multiple Sclerosis lesions is the loss of myelinating oligodendrocytes and demyelination. ProMyelo’s modified cuprizone model shows consistent levels of axonal demyelination providing an excellent platform for qualitative and quantitative readouts of demyelination.
Cuprizone intoxication is one of several animal models used to study demyelination. Early treatment protocols exposed mice to cuprizone for 6 weeks to induce demyelination; however, more recent reports have varied exposure times from 4 to 5 weeks. We found that an abbreviated insult of only 3 weeks of exposure to cuprizone induces oligodedrocyte apoptosis with significant and reproducible demyelination 2 weeks later (5-week time point).
Once mature oligodendrocytes are perturbed after a 3-week treatment, the progression to demyelination occurs without requiring further exposure. This short, “hit and run” model triggers a cascade of events leading to demyelination 2-3 weeks later and is an excellent model to study the development of new therapeutic strategies for treatment of multiple sclerosis.
Experimental End Points
Myelin repair (i.e. remyelination) restores the functional integrity of axons and is neuroprotective. Our remyelination models capture several important attributes of Multiple sclerosis and has been successfully used to test remyelination therapeutics.
The most commonly used models used to study remyelination biology and pathology is the focal Lysophosphatidylcholine-induced Remyelination model and the Cuprizone Remyelination model.
Cuprizone Model of Remyelination
Cuprizone ingestion in mice induces a highly reproducible demyelination of distinct brain regions, among them the corpus callosum which represents the most frequently investigated white matter tract in this animal model. After 5–6 weeks of cuprizone treatment, the Corpus callosum is almost completely demyelinated, a process called ‘‘acute demyelination’’. Acute demyelination is followed by spontaneous remyelination during subsequent weeks when mice are fed normal chow.
In contrast, remyelination is highly restricted when cuprizone administration is prolonged (13 weeks or longer), a process called ‘‘chronic demyelination’’. To study the effectiveness of pharmaceutical substances on myelin repair, acute or chronic demyelination will be induced in mice and animals treated during the recovery period. Test compound can be delivered either per os, intravenously, intraperitonealy, intraventricularily by stereotaxis, or by subcutaneous depot-injections.
ProMyelo offers a complete range of standard and customized neurohistology services. Our specialized histology and immunohistochemistry capabilities combined with our custom analysis techniques provide increased throughput and decreased variability for high quality tissue evaluation. We offer neurohistology either as a complete service or specific expertise to complement your in-house capabilities, including:
High content screening (HCS) to evaluate Oligodendrocyte precursor cell (OPC) differentiation.
Endogenous remyelination of axons occurs in the central nervous system (CNS) of Multiple Sclerosis (MS) patients, however, this regenerative process is sometimes inefficient and decreases as the disease progresses. Remyelination not only restores proper axonal conduction, but also protects axons from degeneration. Improving remyelination efficiency therefore directly exerts neuroprotection and halts disease progression. For remyelination to occur, oligodendrocyte progenitor cells (OPC) must survive and proliferate, differentiate into mature oligodendrocytes and then produce new myelin sheaths.
ProMyelo offers cell-based assays to identify and evaluate compounds that stimulate OPC proliferation and differentiation. Differentiation of OPC is analyzed using state of the art methods such as quantification of morphological characteristics, immunocytochemistry, western blotting, and analyses of gene expression levels. Proliferation of OPC is addressed using standard proliferations assays or the advanced xCelligence system (Roche Applied Science).
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SRC ProMyelo has not received any endorsements.