Publication Demonstrates the Feasibility to Use Blood Biomarkers to Monitor Response to ANAVEX®2-73 (blarcamesine) in Clinical Trials of Fragile X Syndrome (Major Cause of Autism)
NEW YORK – June 8, 2022
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) disorders, today announced the peer-reviewed publication in American Journal of Medical Genetics identifying a blood biomarker for assessing treatment effect of ANAVEX®2-73 in Fragile X Syndrome, which will be also included in the planned clinical trial of ANAVEX®2-73 in Fragile X Syndrome.
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. 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).  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.
“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."
The paper can be accessed online at: https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.62853
Anavex Life Sciences’ product portfolio platform includes orally available small molecule drug lead candidate ANAVEX®2-73 for the treatment of Alzheimer’s disease, Parkinson’s disease and Rett syndrome and ANAVEX®3-71 for frontotemporal dementia.
About Fragile X Syndrome and Autism Spectrum Disorder
Fragile X Syndrome is the most common form of inherited intellectual disability and the most frequent single gene cause of autism, affecting approximately 1 in 4,000 males and 1 in 6,000 females. The disorder is caused by the unstable expansion of a CGG repeat in the FMR1 gene that leads to abnormal methylation and suppression of FMR1 transcription with the resulting decrease in protein levels in the brain and other tissues. The average age of Fragile X Syndrome diagnosis for boys and girls are 35 to 37 months and 42 months, respectively. Behavioral abnormalities, including autism spectrum disorder, are common.
Autism spectrum disorder is a behavioral diagnosis while Fragile X Syndrome is a medical/genetic diagnosis. Many studies have evaluated the link between Fragile X Syndrome and autism spectrum disorder over the last few decades. Since many children with Fragile X Syndrome are interested in social interactions, they may not meet the diagnostic criteria for autism spectrum disorder, even though they exhibit some features such as poor eye contact, shyness, social anxiety, hand-flapping and sensory issues. Autism is much more common in boys than in girls with Fragile X Syndrome. According to the CDC, a national parent survey found that 46% of males and 16% of females with Fragile X Syndrome have been diagnosed or treated for autism spectrum disorder.
About FRAXA Research Foundation
FRAXA’s mission is to find effective treatments and ultimately a cure for Fragile X Syndrome. FRAXA directly funds research grants and fellowships at top universities around the world. FRAXA partners with biomedical and pharmaceutical companies, large and small, to bridge the gap between research discoveries and actual treatments. Treatments for Fragile X Syndrome are likely to help people affected by autism, Alzheimer’s, and other brain disorders. More information is available at www.fraxa.org.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex’s lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a clinical trial for Alzheimer’s disease, a Phase 2 proof-of-concept study in Parkinson’s disease dementia and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson’s Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson’s disease. ANAVEX®3-71, which targets sigma-1 and muscarinic M1 receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the company on Twitter, Facebook,Instagram and LinkedIn.
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Email: firstname.lastname@example.org  https://fragilex.org/understanding-fragile-x/fragile-x-101/prevalence/  https://www.nature.com/articles/s41598-021-94079-7  Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as Therapeutic Targets.