Tuesday, 18 November 2014

Screening for remyelination

Peppard JV, Rugg CA, Smicker MA, Powers E, Harnish E, Prisco J, Cirovic D, Wright PS, August PR, Chandross KJ. High-Content Phenotypic Screening and Triaging Strategy to Identify Small Molecules Driving Oligodendrocyte Progenitor Cell Differentiation. J Biomol Screen. 2014. pii: 1087057114559490. [Epub ahead of print]

Multiple Sclerosis is a demyelinating disease of the CNS and the primary cause of neurological disability in young adults. Loss of myelinating oligodendrocytes leads to neuronal dysfunction and death and is an important contributing factor to this disease. Endogenous oligodendrocyte precursor cells (OPCs), which on differentiation are responsible for replacing myelin, are present in the adult CNS. As such, therapeutic agents that can stimulate OPCs to differentiate and remyelinate demyelinated axons under pathologic conditions may improve neuronal function and clinical outcome. We describe the details of an automated, cell-based, morphometric-based, high-content screen that is used to identify small molecules eliciting the differentiation of OPCs after 3 days. Primary screening was performed using rat CG-4 cells maintained in culture conditions that normally support a progenitor cell-like state. From a library of 73,000 diverse small molecules within the Sanofi collection, 342 compounds were identified that increased OPC morphological complexity as an indicator of oligodendrocyte maturation. Subsequent to the primary high-content screen, a suite of cellular assays was established that identified 22 non-toxic compounds that selectively stimulated primary rat OPCs but not C2C12 muscle cell differentiation. This rigorous triaging yielded several chemical series for further expansion and bio- or cheminformatics studies, and their compelling biological activity merits further investigation.

So Big Pharma are in the hunt for remyelinating factors also, GSK are off the block and are in clinical trial already, Genzyme-Sanofi are other MS pharma and they have found a number (22) of compounds in a number of  (seven) of series of compounds. What are they..they don't say and what do they bind to..they don't say.

We will have to wait an see....frustrating

3 comments:

  1. This is a comment regarding the italian knights psot above. I would love to tick a box statign 'unhelpful' for these psots, but no option is available. Mouse has been let out (thanks to Prof G's extended holiday). He is off to Italy to talk about EAE (boring!). Not slumming it: "Grand Hotel Dino is a 4 star hotel located in Baveno, a town on the west shore of Lago Maggiore in Italy." No doubt there will be a comment from Mouse bemoaning the early flight, long hours etc. etc. Enjoy it while you can Mouse. In 4 months time the big cheese will be abck and your foreign jollies will be over. Bring back something nice for MD 2 - the only one who does much work these days.

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    1. Grand Hotel Dino is indeed very nice, we went to a cannabis meeting there in the summer. Lovely, one of the best work trips I've been on. However, as you may have heard there has been a huge amount of rain in the area recently and Lake Maggiore is flooding so might not be as pleasant as you suggest.
      Something nice from the ceramics shop on Isla Bella would be nice! ;-)
      Working hard as always!

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    2. I have been let out.....twice in a couple of weeks...

      FYI The lack of "unhelpful" was in response to our dear CCSVIers

      In contrast to what you think, not an early flight but after a days work have you got me GPS tagged, sounds like I am being stalked :-).

      As to long hours. Yep, getting ready for my "boring" talk has taken quite a few hours preparation.

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