One of the fastest growing markets in healthcare is the field of neuropathic pain therapeutics. Neuropathic pain is the sensation of pain caused by damaged or dysfunctional nerves sending incorrect signals to the brain’s pain centers. Potential causes of neuropathic pain are many and varied, ranging from cancer and cancer treatments, to strokes and surgery, to infections and even alcoholism. It’s a complex field, and the treatment of neuropathic pain is a multi-billion market, expected to grow at over 9% annually to potentially $10 billion by 2018.
There are currently a limited number of therapies for dealing with neuropathic pain, which provide only partial pain relief and do not effectively address the underlying cause of the pain. The need now is for something that is more effective, with less safety concerns. One of the challenges in dealing with neurological problems is getting effective drugs across the blood-brain barrier. For example, 7-Chlorokynurenic acid (7-Cl-KYNA) is one of the most potent and specific glycineB (GlyB) site antagonists currently known, important for dealing with pain and other issues. When injected directly into the brain, 7-Cl-KYNA is known to reduce seizures, excitotoxic and neuronal death. But, like almost all existing GlyB antagonists, 7-Cl-KYNA does not cross the blood-brain barrier, and is ineffective following peripheral administration. AV-101 readily crosses the blood-brain barrier and is then efficiently converted into 7-chlorokynurenic acid (7-Cl-KYNA), one of the most potent and specific glycineB site antagonists currently known, and has been shown to reduce seizures and excitotoxic neuronal death.
VistaGen Therapeutics’ lead drug candidate, AV-101, is currently under development as a new orally available treatment for neuropathic pain. AV-101 is a prodrug (4-Cl-KYN) of 7-Cl-KYNA. The important difference between the two is that 4-Cl-KYNA is able to readily cross the blood-brain and is then efficiently converted into 7-Cl-KYNA. In other words, like a Trojan horse, AV-101 can sneak its way into the brain, overcoming the blood-brain barrier. Once inside, it changes into a highly potent new form (7-Cl-KYNA), which, VistaGen believes, will enable it to become an effective treatment for a widespread medical problem.
In preclinical studies, AV-101 has been shown to have a positive effect on chronic neuropathic pain, with no observed adverse behavioral effects. It has shown greater than 90% oral bioavailability, and is rapidly and efficiently transported across the blood-brain barrier where it is converted into 7-Cl-KYNA in the brain and spinal cord – preferentially at the site of seizures and potential neural damage. Moreover, VistaGen’s development plan for AV-101 has been designed to allow Phase 1 safety studies to support potential Phase 2 development for any additional neurological indications (such as epilepsy, Parkinson’s disease, Huntington’s disease, and depression) for which there is supporting efficacy information. To date, VistaGen has been awarded over $8.5 million from the U.S. National Institutes of Health for preclinical and clinical development of AV-101.
For additional information, visit the company’s website at www.VistaGen.com
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