One of the most notable properties of AV-101 is its ability to essentially trick the body into letting it get past the formidable blood-brain barrier, a separation of the body’s blood circulation from the brain extracellular fluid in the central nervous system. The blood-brain barrier has long represented a major obstacle for drug manufacturers seeking ways to treat nerve and brain related diseases. Because of its extraordinary chemical design, AV-101 is able to readily cross this barrier. It is then converted into a variation of itself, a chemical which does the work needed to be done, such as relieving neuropathic pain. AV-101’s development plan is such that it can allow Phase 1 safety studies to support potential Phase 2 development for the treatment of other neurological conditions, such as epilepsy, Parkinson’s disease, Huntington’s disease, and depression.
AV-101 highlights include the following:
• Readily crosses the blood-brain barrier
• Anticonvulsant that protects against NMDA receptor-mediated neurotoxicity
• Preferentially converted to the GlyB antagonist, 7-Cl-KYNA, by activated glial cells at the desired sites of therapeutic action, thereby reducing the potential risk of side effects even in chronic treatment regimens
• A pro-drug with no therapeutic activity until metabolic conversion
• Generates therapeutically-meaningful brain levels of 7-Cl-KYNA with oral administration
• Converted to 4-Cl-3-hydroxyanthranilic acid, which blocks the synthesis of quinolinic acid (an endogenous convulsant and NMDA receptor agonist) which may further reduce glutamatergic toxicity associated with epilepsy and other neurodegenerative diseases
• Antagonists of the GlyB site, such as 7-Cl-KYNA, have a favorable safety profile compared to other NMDA receptor antagonists
• May stimulate the expression and/or development of dopamine positive neurons
• Comparable efficacy to gabapentin in three animal models of neuropathic pain
For additional information, visit the company’s website at www.VistaGen.com
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