My thoughts on the OPC assay:
Multiple Sclerosis (MS) in a chronic inflammatory demyelinating disease of the central nervous system. As we know, myelin is a substance rich in fatty substances and proteins that surrounds the axon of some nerve cells. In MS, Myelin of the CNS is produced by cells called oligodendrocytes. In MS, there is an abnormal immune system response which causes inflammation in the CNS and essentially destroys and/or damages myelin and oligodendrocytes. Mouse studies have shown that lack of oligodendrocytes near MS lesions may cause a deficiency in remyelination of the nerve (FYI, this is a simplified view of a complex disease, but important background information).
Anavex just did a material transfer to Biogen for Biogen to study 2-73 in a neurological protection model. Essentially, they will be testing 2-73 in an oligodendrocyte precursor cell (OPC) differentiation assay. Oligodendrocytes arise from OPCs which are present within the brain and spinal cord. Therefore, since Oligodendrocytes are damaged in MS due to inflammation, and also since OPCs are found around lesions but still fail to repair myelin do, it is an area of interest to study how OPCs can differentiate into oligodendrocytes to promote remyelination in MS. They may believe 2-73 is an important mediator of OPC differentiation into oligodendrocytes. What you can do is put OPCs in a dish, either with or without 2-73, and see if they differentate into oligodendrocytes by then using a fluorescent antibody to specifically stain for oligodendrocytes and detecting the differences in numbers between treatment and control using machines that have powerful lasers. (One way of doing an OPC differentiation assay).
Also, oligodendrocytes migrate through a mesh work of astrocytes to get to the lesions that have been demyelinated. Therefore, I think they may want to study migration as well. You can study this migration using an in vitro assay (essentially in a dish). I'm assuming they will use a dish that has chambers separated by pores. What you can do in this type of assay is put the OPCs in one chamber, and then put the chemoattractant (I'm wondering if 2-73 may aid in this chemoattractant process) into the dish - either the opposite chamber or also where the pores are, depending on how they want to design the experiment - and when comparing it to a dish that doesn't have the chemoattractant, you can see if the OPCs migrate in response to the attractant (2-73 in this case) by counting the number of cells in the opposite chamber. For what it's worth, these experiments do not take much time at all.
If results are good, Biogen will want to move forward with a in vivo remyelination study using a chemical demyelination model (in mice). In these models, they will most likely administer a compound called Cuprizone, a copper chelator which leads to oligodendrocyte death and subsequent spontaneous but reversible demyelination. When you stop administering Cuprizone, remyelination can start within 4 days and is completed in 3-5 weeks. This model is ideal for testing hypotheses about what might hinder remyelination in MS patients, or what may improve it. I believe they may use this model to test 2-73 in vivo.
Just some thoughts, feel free to discuss/argue/confirm my ideas.
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