Thursday, 11 July 2013

EAE in Primates


Haanstra KG, Jagessar SA, Bauchet AL, Doussau M, Fovet CM, Heijmans N, Hofman SO, van Lubeek-Veth J, Bajramovic JJ, Kap YS, Laman JD, Touin H, Watroba L, Bauer J, Lachapelle F, Serguera C, 't Hart BA.Induction of Experimental Autoimmune Encephalomyelitis With Recombinant Human Myelin Oligodendrocyte Glycoprotein in Incomplete Freund's Adjuvant in Three Non-human Primate Species. J Neuroimmune Pharmacol. 2013 Jul 3. [Epub ahead of print]

The experimental autoimmune encephalitis (EAE) model is used for preclinical research into the pathogenesis of multiple sclerosis (MS), mostly in inbred, specific pathogen free (SPF)-raised laboratory mice. However, the naive state of the laboratory mouse immune system is considered a major hurdle in the translation of principles from the EAE model to the MS patient. Non-human primates (NHP) have an immune system harboring T- and B-cell memory against environmental antigens, similar as in humans. We sought to further refine existing NHP EAE models, which may help to bridge the gab between mouse EAE models and MS. We report here on new EAE models in three NHP species: rhesus monkeys (Macaca mulatta), cynomolgus monkeys (Macaca fascicularis) and common marmosets (Callithrix jacchus). EAE was induced with recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG) formulated in incomplete Freund's adjuvant (IFA). IFA lacks the bacterial antigens that are present in complete Freund's adjuvant (CFA), which are notorious for the induction of discomforting side effects. Clinically evident EAE could be induced in two out of five rhesus monkeys, six out of six cynomolgus monkeys and six out of six common marmosets. In each of these species, the presence of an early, high anti-rhMOG IgM response is correlated with EAE with an earlier onset and more severe disease course. Animals without an early high IgM response either did not develop disease (rhesus monkeys) or developed only mild signs of neurological deficit (marmoset and cynomolgus monkeys).

Well this study says we should definately say "SCHTOP" with regard to trying to induce disease in rhesus macaque as it is not reliable. To develop a drug it must go through toxicology in two different species, some companies like to test stuff in primates prior to going into man, but one has to ask the question is their real value in doing work in primates, as it does not necessarily improve prediction of whether agents will work in human.  Perhaps if there is a safety issue that needs addressing then there may be value.

There are only a few places in the world where this work can and is done. There is no MS primate work done in the UK.

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