Anavex Life Sciences Corp (AVXL)

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Fun with neurons.

Potential Therapy, Anavex 2-73, Shows Ability to Protect Neurons and Promote Myelin in Early Tests

Anavex Life Sciences‘ investigational therapy Anavex 2-73 (blarcamesine) showed an ability to protect, repair, and induce the formation of oligodendrocytes — the cells that produce the protective myelin layer around neurons — in early cell testing, researchers reported.

These findings, which further establish the therapy’s potential as a treatment for multiple sclerosis (MS), were described in the study “Sigma-1 receptor agonists as potential protective therapies in multiple sclerosis” published in the Journal of Neuroimmunology.

MS, a neurodegenerative disease, is characterized by the loss of myelin (demyelination) — the protective fatty layer surrounding nerve cells— as well as inflammation and the loss of oligodendrocytes.

Oligodendrocytes are the cells responsible for producing myelin in the central nervous system (CNS). MS is marked both by the loss of myelin and defective remyelination, a process that involves the increased proliferation of oligodendrocyte precursor cells (OPCs) and their maturation into myelin-producing oligodendrocytes.

While effective disease-modifying therapies (DMTs) are known to slow MS progression, they can have significant side effects and patients can still experience disease worsening.

“Thus, additional therapies are needed to provide direct protection to CNS cells like OL [oligodendrocytes], OPC, and neurons as well as to support or induce reparative processes,” the researchers wrote.

Anavex 2-73 is designed to activate the sigma-1 receptor (S1R), which is essential for the proper folding of proteins within nerve cells and to neuroplasticity — the brain’s ability to adapt or form new connections and pathways as, for example, a response to aging or injury. Anavex 2-73 is also thought to decrease a number of harmful events implicated in MS, such as brain inflammation and oxidative stress.

Researchers at Wayne State University School of Medicine assessed Anavex 2-73’s effects in a series of in vitro (outside a living organism; cells in the lab) tests.

They exposed oligodendrocytes to four cytotoxic agents: glutamate (induces neuronal toxicity), staurosporine (induces cell death), H2O2 (induces oxidative stress), and quinolinic acid (induces inflammation). These killed 60% to 70% of mature oligodendrocytes over 24 hours.

These agents were chosen because they represent “several pathogenic [disease-causing] mechanisms underlying white matter damage in MS,” the researchers wrote.

Treatment with Anavex 2-73 was seen to significantly prevent the death of oligodendrocytes caused by all four agents. Furthermore, this protective effect was confirmed to be a direct result of S1R activation.

Researchers also found that these protective effects extended to OPCs, the precursor cells of oligodendrocytes. Anavex 2-73’s use also increased the rate of OPC proliferation by nearly three times, to 46% compared to 16% in cell cultures not given this therapy.

Anavex 2-73, however, did not speed the maturation of OPCs into oligodendrocytes, but there was a trend into that direction, the researchers reported.

Importantly, Anavex 2-73 also protected neurons from the toxicity induced by the four agents tested.

“A unique feature of Anavex 2-73 (blarcamesine), compared to another sigma-1 receptor agonist we studied [dextromethorphan], is that while these molecules increase proliferation of oligodendrocyte precursor cells (OPCs), Anavex 2-73 (blarcamesine) does not inhibit the maturation of these OPCs to oligodendrocytes,” Robert P. Lisak, MD, a professor at Wayne State University School of Medicine and lead author of the study, said in an Anavex press release.

“This is an important feature since OPCs can replace lost OLs [oligodendrocytes] by maturing into new potential myelin-producing cells. In other words, Anavex 2-73 (blarcamesine) might promote remyelination by both providing more OPCs and not delaying their maturation into mature OLs,” Lisak added.

“Further data also demonstrates that Anavex 2-73 (blarcamesine) provides protection for OLs, OPCs, as well as central nervous system neurons in addition to helping repair.”

Christopher U. Missling, PhD, president and CEO of Anavex, concluded: “MS is a lifelong disease that has a significant impact on the people affected and their caregivers. We are encouraged by these findings providing additional evidence for the neuroprotective and neurorestorative effects of Anavex 2-73 (blarcamesine), as well as further expanding its potential application.”

The U.S. Patent and Trademark Office recently issued a patent the therapeutic methods based on Anavex 2-73 for the treatment of several neurodegenerative and neurodevelopmental conditions, including MS.

Anavex 2-73 is currently being evaluated in clinical trials as a possible treatment for Rett syndrome, Alzheimer’s disease, and Parkinson’s disease dementia.

Margarida Azevedo, MSc
Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

Fact Checked By:
Patricia Silva, PhD
Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

https://multiplesclerosisnewstoday.com/news-posts/2020/02/24/anavex-life-sciences-announces-publication-of-foundational-data-for-anavex2-73-blarcamesine-in-multiple-sclerosis-ms