Anavex Life Sciences Corp (AVXL)

[Investor2014]

Does this wealth of microbiome data explain what's taking so long in the rett syndrome readout?

Gut microbiome is an interesting question that has merit also in Rett. However, at least the published AVATAR protocol does not include gut microbiome analysis nor has it been mentioned, as far as I know, outside of the PDD OLE and AD P2b/3 studies.

The Molecular Functions of MeCP2 in Rett Syndrome Pathology

A 2016 study found that Mecp2 null mice had gut hypomotility and reduced nitric oxide synthase expression in enteric neurons (Wahba et al., 2015). To examine the hypothesis that microbial alterations underlie intestinal defects, the overall gut microbiome diversity was examined and appeared to be reduced in Rett patients (Strati et al., 2016; Borghi et al., 2017). As the diets were similar between the Rett and control subjects, these results suggest that altered MECP2 levels in the digestive tract may alter the intestinal environment and thus microbe growth. In fact, it was recently shown that mice with loss of Mecp2 expression solely in the intestine have severe colonic epithelial defects (Millar-Büchner et al., 2016). As there is direct signaling from the gut to the brain, extension of these gut/microbiome studies should be extended to Bird Mecp2–/+ deficient female deletion mice and would thus provide critical insights for female Rett patients. While studies on the role of MeCP2 function in tissues outside of the brain, a recent study found evidence that MeCP2 represses LINE-1 activity in brain, but not in peripheral tissues such as heart and eye (Zhao et al., 2019).