Paper - Brain cell signaling abnormalities are detected in blood in a murine model of Fragile X syndrome and corrected by Sigma-1 receptor agonist Blarcamesine
Fragile X syndrome paper
Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and the most frequent single gene cause of autism spectrum disorder with an estimated population of approximately 62,500 in the US and 1,088,500 worldwide.1 At present, there is no approved treatment for Fragile X Syndrome.
The findings demonstrate that treatment effect of ANAVEX®2-73 resulting in reversal of hyperactivity, restoration of associative learning and reduction of anxiety in a mouse model of Fragile X Syndrome are also associated with improvements in key blood signaling biomarkers, which are measurable in patients with Fragile X Syndrome as well.
Previously reported improvements in cognitive and behavioral paradigms in a mouse model of Fragile X Syndrome, after ANAVEX®2-73 administration, are associated with parallel improvements in peripheral lymphocyte signaling abnormalities (i.e., decrease in activated/phosphorylated Akt and ERK).2 Fragile X Syndrome is characterized by multiple cell signaling abnormalities, including increased activation of the PI3K/Akt/mTOR and MAPK/ERK pathways. These have been demonstrated in brain samples from mouse models as well as in lymphocytes from patients.
The present publication, “Brain cell signaling abnormalities are detected in blood in a murine model of Fragile X syndrome and corrected by Sigma-1 receptor agonist Blarcamesine,” is one of the first studies showing that key signaling abnormalities can also be detected and corrected in mouse lymphocytes, providing a solid foundation for the use of lymphocyte signaling biomarkers in clinical trials involving ANAVEX®2-73. The study was supported by the FRAXA Research Foundation.
“Evaluations of lymphocyte cell signaling in mouse models of Fragile X Syndrome are feasible and support corresponding assessments in affected individuals,” said Walter E. Kaufmann, M.D., Chief Scientific Officer of Anavex and corresponding author of the publication. “These analyses have the potential for monitoring response to treatment, particularly for drugs correcting multiple pathway abnormalities such as sigma-1 receptor agonist ANAVEX®2-73. Implications of this work extend beyond FXS to most neurologic disorders associated with abnormal cell signaling.”
Data suggests that activation of the sigma-1 receptor is pivotal to restoring neural cell homeostasis and promoting neuroplasticity.3
“These additional biomarker findings in Fragile X Syndrome provide further evidence of potential to expand the therapeutic profile of ANAVEX®2-73 into the largest portion of addressable market of autism spectrum disorder, Fragile X Syndrome,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “We look forward to initiating a double-blind, placebo-controlled Phase 2/3 ANAVEX®2-73 study in Fragile X Syndrome. This is further evidence of the potential of ANAVEX®2-73 as a platform technology of precision medicine." |
