Thursday, 9 March 2017

Remyelination

Medina-Rodríguez EM, Bribián A, Boyd A, Palomo V, Pastor J, Lagares A, Gil C, Martínez A, Williams A, de Castro F. Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis. Sci Rep. 2017;7:43545

Multiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action. The dual inhibition is synergistic, as increasing intracellular levels of cAMP by cyclic nucleotide PDE inhibition both suppresses the immune response and increases remyelination, and in addition, inhibition of GSK3 limits experimental autoimmune encephalomyelitis in mice. This combination of an advantageous effect on the immune response and an enhancement of repair, plus demonstration of its activity on adult human OPCs, leads us to propose dual PDE7-GSK3 inhibition, and specifically VP3.15, as a neuroprotective and neuroreparative disease-modifying treatment for MS.


Another experimental remyelination treatment

7 comments:

  1. Can you add one of yourvery valuable, to us non-scientists, commentaries Pleeease??

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    1. PDE7 inhibitors are sometimes reported to inhibit EAE. PDE4 inhibitors also block cyclic AMP and block TNF and inhibit EAE but can make MS worse. PDE5 inhibitor is viagra. GSK3 inhibition inhibits EAE, so it is immunosuppressive but is it good enough to go head to head with one of them as this is unlikely to be an add on with two immunosuppressives.

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    2. So not sure how it will be developed

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  2. Hate to be negative, but I will be. Remyelination has not been shown in humans to do anything. Anti LINGO failed and whatever happened to MSCs? The only investigative treatment that has shown reversal of established disability in progressive MS is NPCs. Why don't we focus on that ? Why do we continue to pursue blind leads?

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  3. Replies
    1. OPC but one letter backwards

      I guess N equals Neural maybe neural stem cells

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    2. Neural progenitor cells, here in US parlance, derived from MSCs

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