This looks important but I need help to understand it.

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frodo
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This looks important but I need help to understand it.

Post by frodo » Wed Apr 08, 2020 2:23 am

This paper looks important. They have even made a video to explain it, but I cannot understand it. If anyone of you knows what are they talking about I would appreciate a summary in plain english.

https://ars.els-cdn.com/content/image/1 ... 6-mmc4.mp4

Summary

https://www.sciencedirect.com/science/a ... 7420302646

Multiple sclerosis (MS) is an autoimmune disease characterized by attack on oligodendrocytes within the central nervous system (CNS). Despite widespread use of immunomodulatory therapies, patients may still face progressive disability because of failure of myelin regeneration and loss of neurons, suggesting additional cellular pathologies. Here, we describe a general approach for identifying specific cell types in which a disease allele exerts a pathogenic effect. Applying this approach to MS risk loci, we pinpoint likely pathogenic cell types for 70%. In addition to T cell loci, we unexpectedly identified myeloid- and CNS-specific risk loci, including two sites that dysregulate transcriptional pause release in oligodendrocytes. Functional studies demonstrated inhibition of transcriptional elongation is a dominant pathway blocking oligodendrocyte maturation. Furthermore, pause release factors are frequently dysregulated in MS brain tissue. These data implicate cell-intrinsic aberrations outside of the immune system and suggest new avenues for therapeutic development.

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Scott1
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Re: This looks important but I need help to understand it.

Post by Scott1 » Wed Apr 08, 2020 4:49 am

Hi,

It's not quite as groundbreaking as it sounds. Loci is a fancy name for genetic markers and coding genes.
If you stretched out a string of DNA it would be massively long. So it can squeeze into a small space it winds around proteins called histones. If the histone has the opposite charge to the DNA they bind tightly together, too tightly for anything else to bind. (In the same way as two differing poles on magnets draw together.) Genes that nothing else can bind to are turned "off". There are range of processes that cause the binding to loosen. This can turn genes "on". An example of a gene that gets a lot of attention in MS is called HLA-DR1501. It is one of many. They are saying they can identify others.
They are saying they can identify genes that interact with T cells, genes that can interact with Dendritic cells and genes that cause the cells that make myelin (the oligodendrocytes) to pause or fail . Without telling us that they have found anything new, they are suggesting that using their techniques opens up the possible number of target genes. Some of these genes have nothing to do with the normal immune function so any therapy targeting these targets would work differently than most currently on the market.
Regards,

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Re: This looks important but I need help to understand it.

Post by frodo » Sat Apr 11, 2020 3:15 am

Thank you. I was expecting something more concrete, but it is interesting anyway.

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