Its use also helped to lessen abnormal movements and ease breathing in these mice, its researchers said.
The study, “ANAVEX®2-73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome,” was published in the journal Pharmacology Biochemistry and Behavior.
Anavex 2-73 (blarcamesine) is an oral investigational therapy developed by Anavex Life Sciences that works by activating the sigma-1 receptor (S1R), a protein involved in the correct folding of other proteins.
S1R activation results in reduced toxic accumulation of misfolded proteins, as well as lesser dysfunction in mitochondria (a cell’s “powerhouse”), oxidative stress and neuroinflammation, all involved in Rett syndrome. (Oxidative stress is an imbalance between the production of free radicals — potentially harmful molecules associated with a number of diseases — and the generation of antioxidant defenses.)
They assessed motor function (balance, motor coordination, locomotion, and abnormal movements or stereotypies), sensory function (reflex responses to sound stimuli and visual clarity), and respiratory function.
Motor and sensory functions were assessed in younger mice, while visual acuity and breathing were measured in older animals.
Results showed that Anavex 2-73 significantly eased motor dysfunction, and deficits in acoustic and visual responses compared to mice given a placebo.
Anavex 2-73 also induced a significant reduction in two distinctive features of Rett syndrome found in these mice: hind-limb clasping (an abnormal posture comparable to hand stereotypies in people with Rett), and apnea (involuntary breath-holding) that is the most concerning breathing abnormality in Rett syndrome, the researchers said. These improvements were mainly dependent on treatment dose and duration.
“In conclusion, the data demonstrate that [Anavex 2-73] is effective in ameliorating multiple neurobehavioral phenotypes in [Rett] mice,” the researchers wrote. “In line with previous animal and human studies [in other neurodegenerative diseases], [Anavex 2-73] also showed a good safety profile,” they added.
These data served as a proof-of-concept for an ongoing safety and efficacy Phase 2 trial called RS-001 (NCT03758924, still enrolling) in the U.S., and for the Phase 2 AVATAR study (NCT03941444) in Australia. These trials together will evaluate Anavex 2-73 in up to 51 women with Rett syndrome.
Preliminary results from the first six participants in RS-001 showed that Anavex 2-73 was well-tolerated and significantly eased Rett symptoms. These benefits were associated with consistent changes in blood levels of key biomarkers of the disorder.
The company recently announced plans to soon launch a placebo-controlled clinical trial called EXCELLENCE, which will investigate the safety and effectiveness of Anavex 2-73 in about 69 children and adolescents (ages 5 to 18) with Rett syndrome.
The trial is expected to open in Australia in the coming months, followed by clinical sites in countries worldwide. More information is available by clicking here.
“Testing novel drugs that can safely improve the symptoms of Rett syndrome is a high priority,” Walter E Kaufmann, MD, the preclinical study’s lead author and chief medical officer of Anavex, said in a press release.
Christopher U. Missling, PhD, Anavex’s CEO, added his company “is excited about our progress to date, as well as our pursuit of a much-needed treatment option for patients with Rett syndrome.”
Anavex-2-73 was designated an orphan drug by the U.S. Food and Drug Administration in January 2017 as a potential Rett treatment. The European Medicines Agency’s Committee for Orphan Medicinal Products has recommended a similar designation from the European Commission.