Anavex Rett Science Is Good
Thanks for posting this URL, for this most important paper.
Here’s the abstract. I’ve color-marked the important facts for those of us who hold an AVXL position.
BACKGROUND: The Sigma-1 receptor (s1R) is an intracellular chaperone protein located at the endoplasmic reticulum - mitochondria interface with important roles in inter-organelle communication and the cellular response to stress. ANAVEX 2-73 (AV2-73) is a s1R agonist that has previously demonstrated favorable safety, bioavailability, and tolerability in Phase 1/2 clinical trials. Data from the ongoing Phase 2a study in Alzheimer’s disease patients demonstrate signs of dose-dependent cognitive improvement.
Given the reported ability of the s1R to restore cellular functionality, neurodevelopmental disorders may respond to the activation of s1R in a disease-modifying manner. One such disorder is Rett syndrome and the MECP2 HET mouse is a well-characterized model with a behavioral profile that mimics many aspects of the clinical picture.
METHODS: Female MECP2 HET and wild type (WT) mice were used throughout (N=19-20 per treatment arm). Chronic daily dosing of AV2-73 (10 or 30 mg/kg/day PO) starting at 5.5 weeks of age was conducted throughout a 12-week period of testing. Behavioral paradigms measured different aspects of motor coordination, reflex reactivity, and species-specific behavior (clasping). In a separate study, 4 weeks of daily dosing starting at 6.5 months of age was followed by optokinetic analysis of relative visual acuity and changes in respiration by whole body plethysmography. Significance at p<0.05 was determined by ANOVA and post-hoc comparisons.
RESULTS / DISCUSSION: In the younger cohort of mice, chronic dosing with AV2-73 significantly improved performance of the MECP2 HETs in different motor and gait paradigms, and reduced clasping behavior to WT levels. Among the older cohort, relative visual acuity in AV2-73-treated HET mice was returned to WT levels at the slower rotating speed. A reduction in apnea counts (~35%) relative to WT levels was observed in HETs receiving AV2-73.
CONCLUSIONS: AV2-73 significantly improves an array of behavioral phenotypes in the Rett syndrome mouse model in a dose-related manner. Based on these data, Anavex Life Sciences will start a U.S. multicenter Phase 2 clinical trial of AV2-73 for the treatment of Rett syndrome with the support of Rettsyndrome.org.
