CHSG has developed a partnership with CuresWithinReach to leverage their novel CureAccelerator platform for research collaboration across researchers, biotechnology, and pharma. We are very excited about this opportunity to bring all relevant parties together under a single collaborative environment, and actually have already had good success! Onward to the CURE!
Selective TRP Channel antagonists for Primary Headache
There is a remarkable alignment between typical triggers for both Cluster Headache and Migraine with the basic mammalian sensory system called TRP Channels, specifically TRP V1, A1, and M8. This sensory system is completely separate from the typical 5 senses of taste, smell, touch, sight, and hearing, yet is fundamental to survival of all mammals. These sensors ellicit a flinch, blink, or pain response to noxious or otherwise potentially harmful stimuli and are considered a fundamental survival mechanism in the body. These receptors specifically react to bright light, potentially harmful chemical odor, minor temperature and osmotic pressure change, and even such things as hot pepper, mustard oil, garlic, menthol, and fetid odor, ie. potentially harmful organics. They elicit a flinch, blink, and frequently a pain response to these stimuli along the trigeminal nerve complex. (Source: 2015, see mutliple peer-reviewed Medical Journals, CHSG Research Targets)
The etiology of primary headache is largely undetermined; however, there is significant anecdotal evidence of a correlation to known triggers, including temperature and weather change, alcohol, preservatives, chemical smells, vanilloid odors, cigarette smoke, and others, all of which map directly to excitation of the TRP V1, A1, and M8 channels. It is also proven that desensitization of these channels, even with basic homeopathic remedies such as capsaicin (hot pepper) can significantly reduce the incidence of these headaches by desensitizing the channel. We believe there may actually be a causal relationship and that perhaps these channels have become hypersensitive in Cluster Headache and Migraine patients.
There are several biologics and phase II, in human studies of TRP channel agonists-antagonists underway, but for different indications. We would like to leverage these existing efforts to study the potential for a preventive medication or even a cure. Specifically, we are aware of the following very promising candidates: SB-705498, PHE377, JNJ-17203212, Capsazepine, AMG0610, BCTC (Purdue Pharma), A-425619.
Study of Efficacy of NMDA Receptor Antagonists for Primary Headache Treatment
Ketamine Infusion Therapy has recently seen resurgence in the treatment of peripheral nerve pain conditions, including RDS, CRPS, Fibromyalgia, and Phantom Limb Syndrome. As well, ketamine analogues memantine and amantadine have seen broader off-label use in the treatment of Cluster Headache and Migraine. These NMDA receptor antagonists are primarily indicated for Alzheimers disease today; however, with the advent of broad narcotic/opioid abuse and dependence, new regulatory controls have come to the foreground and a need for less addictive pain control options are needed. Both memantine and amantadine are approved for medical use by the FDA. Memantine is also under new formulation under the trade name Namenda and Namenda XR by Forest Laboratories, Inc. Ketamine is proven and frequently used for both anesthetic and analgesic benefit.
Ketamine was approved for medical use by the FDA decades ago and is now available in generic form. A current investigational study is underway at Jefferson Headache Center in conjunction with the Jefferson Pain Management Center. Results thus far are very promising for both immediate and long-term relief. There is a need to further this study to include a broader patient base with additional healthcare centers and outcomes reporting.
Opportunities for reformulation and compounded solutions exist under this new indication, Cluster Headache and other primary headaches, including Migraine. Cluster Headache is a debilitating disorder defined as a neurovascular primary headache disorder by the International Headache Society (IHS) (ICD-10 G44.0). "Attacks of severe, strictly unilateral pain which is orbital, supraorbital, temporal or in any combination of these sites, lasting 15-180 minutes and occurring from once every other day to 8 times a day. The attacks are associated with one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhoea, forehead and facial sweating, miosis, ptosis, eyelid oedema. Most patients are restless or agitated during an attack." (source: 2015, IHS).