Regulating remyelination

He D, Marie C, Zhao C, Kim B, Wang J, Deng Y, Clavairoly A, Frah M, Wang H, He X, Hmidan H, Jones BV, Witte D, Zalc B, Zhou X, Choo DI, Martin DM, Parras C, Lu QR. Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination. Nat Neurosci. 2016 . doi: 10.1038/nn.4258. [Epub ahead of print]

Mutations in CHD7, encoding ATP-dependent chromodomain helicase DNA-binding protein 7, in CHARGE syndrome lead to multiple congenital anomalies, including craniofacial malformations, neurological dysfunction and growth delay. Mechanisms underlying the CNS phenotypes remain poorly understood. We found that Chd7 is a direct transcriptional target of oligodendrogenesis-promoting factors Olig2 and Smarca4/Brg1 and is required for proper onset of CNS myelination and remyelination. Genome-occupancy analyses in mice, coupled with transcriptome profiling, revealed that Chd7 interacted with Sox10 and targeted the enhancers of key myelinogenic genes. These analyses identified previously unknown Chd7 targets, including bone formation regulators Osterix (also known as Sp7) and Creb3l2, which are also critical for oligodendrocyte maturation. Thus, Chd7 coordinates with Sox10 to regulate the initiation of myelinogenesis and acts as a molecular nexus of regulatory networks that account for the development of a seemingly diverse array of lineages, including oligodendrocytes and osteoblasts, pointing to previously uncharacterized Chd7 functions in white matter pathogenesis in CHARGE syndrome.

I’m sorry i don’t have time to do this one justice but suffice to say yet another pro remyelinating factor. One of the many we have heard about in the past couple of years but where are we?

This is not one I am best placed to judge but if it were experimental remyelination, we could give a report as long as your arm, but what about remyelination trials in progress.

1. Stem cell trials
The great Hope…yet all too often the Great HYPE

There are Haematopoeitic stem cells…this has nothing to go with repair. 

Mesenchymal stem cells….There are a few trials..nothing to report but they are tried in relapsing MS.


Because the data in animals shows that the stem cells are immunomodulatory, rather than repairative. Tothers in the pipeline like neural stem cells.

Verdict Promise for the future.

However the GSK trial should have finished and as no report, read into that what you will.

Clemastine trial but should be rpeorted soon

Anti-LINGO trials ongoing

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  • Thanks for update. This is disheartening for any MS patient that has suffered any irreversible damage from MS that is not able to be repaired endogenously. I suppose there is RhigM22 from Acorda and the Mayo Clinic now in phase II trials and Biotin in phase III trials by Medday if the hype is true.

    I am curious as to why Biogen's anti-lingo researchers chose just optic neuritis MS patients in phase II Renew safety and efficacy trials? Is it just easier to measure remyelination than other sites, like the spinal cord, or is it that researchers know that if remyelination is going on in the optic nerve that it is very likely going to do this elsewhere? I guess the upcoming Synergy phase III trials (out later this year?) will answer this.

  • I thought that there were successful trials on SPMS/PPMS patients at Bristol using mesenchymal stem cells – wouldnt this imply they may have a repair function rather than antiinflammatory?

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