As a young man, I was fortunate to achieve great success with the very first product I developed. That product was Zicam. At the time, I thought it was all about the money and accolades. While I knew that I had developed something special, I didn't realize the true significance of the product itself.
That realization came to me when a mother of an eight year old daughter called me one afternoon and told me her daughter had only one lung, suffered greatly from colds and that the colds always led to secondary bacterial infections. Doctors warned that her daughter would ultimately lose the function in her one remaining lung because of the cold infections.
The mom told me that she began religiously administering Zicam to her daughter whenever she started to see any sign of a sniffle and that her daughter had not had a cold in the past two years. As this Mom, crying on the phone, thanked me for saving her little girls life, I realized for the first time what was truly important. Although I had endured years of economic hardship while developing Zicam and preparing it for market, it was absolutely worth it. What a blessing!
In 2010, a friend whose business associate suffered greatly from migraine headaches asked me if I could help his friend. I respectfully declined only to have my friend call me again asking if I could help. Again, I declined. Finally, after several more pleas for help from my friend I agreed to meet with Mr. Farley
When I met Mr. Farley, I was taken back by his demeanor. He was tired, depressed and very frustrated. It seemed the medical establishment had really let him down. He told me that he suffered severe migraine headaches each and every day for the past twenty years. His typical day would start with the beginnings of a migraine headache and by 10 am, he would have unbearable pain. He would take up to three Imitrex a day and even then there was no relief for him.
After meeting Mr. Farley and hearing his story, I decided to look into the migraine headache scientific literature. To say I was surprised at the lack of attention and research funding devoted to this affliction would be a gross understatement. I found it nothing short of appalling that this situation could exist leaving over 36 million people in the United States and 1 billion people worldwide suffering.
Over the next several months, I explored every aspect of migraine and tried to understand its cause. What was readily apparent from the very beginning, was that the widely accepted theories of the cause of migraine headache were flawed. To me, this meant that the approach and therapeutic targets that the drug companies were taking were off the mark. It was a classic case of old theories and dogmatic thinking leading everyone in the wrong direction.
Driven by a strong desire to help Mr. Farley and all migraine sufferers, I developed a theory of the cause of migraines and based on this theory, I developed Migranade Migraine Relief. Soon after, the open label study confirmed what we already knew; Migranade Migraine Relief truly represents a revolutionary breakthrough in the way migraine headaches are treated.
I am blessed to be part of a solution to this problem that not only impacts the sufferers, but their spouses, children and all of those who love and care about them.
As we embark on our quest to provide much needed relief to millions upon millions of migraine sufferers I hope you will join our Migranade Migraine Relief family. I appreciate you taking the time to read this message, thank you.
Charles B. Hensley, Ph.D.
Chairman and CEO
MIGRANADE, INC. pursuing an agreement with the UNITED STATES ARMED FORCES for inclusion of MIGRANADE Migraine Relief as an issuance to all active military personnel.
Dr. Charles B. Hensley's discovery of the cause and propagation of migraine headaches
A PROPOSED ROLE FOR ACUTELY DIMINISHED LEVELS OF INTRACELLULAR REDUCED GLUTATHIONE (GSH) IN THE GENESIS AND PROPRAGATION OF MIGRAINE HEADACHES
Charles B. Hensley, Ph.D.
Los Angeles, California
Migraine headache is a common disorder afflicting an estimated 36 million people (12% of the general population) in the United States (1) and over 1 billion people worldwide. The estimated annual costs for the United States alone totals in excess of 17 billion dollars, which includes costs of medications; office, clinic, or emergency department visits; laboratory and diagnostic services; management of treatment side effects and lost productivity in the workplace (2).
According to the World Health Organization, migraine headaches are a major cause of disability worldwide, imposing burdens that include substantial personal suffering, reduced quality of life. Repeated headache attacks, and often fear of future attacks, damage family life, social life, and employment (3). Migraines are more prevalent in women with one out of every six women reporting experiencing migraines and the incidence of migraines is thought to be under-reported due to the social stigma associated with migraines. There is also evidence suggesting athletes and military personnel are at increased risk of migraine after suffering head injuries.
The current OTC medications used for treating migraines include ibuprofen (Advil, Motrin, others) or acetaminophen (Tylenol, others) and combination drugs such as Excedrin Migraine. These medications are not effective for severe migraines and if taken too often or for long periods of time, these medications can lead to ulcers, gastrointestinal bleeding and rebound headaches (4).
Prescription medications include sumatriptan (Imitrex), rizatriptan (Maxalt), almotriptan (Axert), naratriptan (Amerge), zolmitriptan (Zomig), frovatriptan (Frova) and eletriptan (Relpax). These medications are expensive, are not always effective, are slow to act, and have serious side effects. Side effects include nausea, dizziness and muscle weakness and they aren't recommended for people at risk for strokes and heart attacks.
It is my contention that the underlying reason that prescriptive and over-the-counter medications for migraine headache have limited efficacy and cause undesirable side effects is due in large part to a general lack of understanding of the etiology of the disease.
In this paper, I put forth a novel hypothesis for the primary cause of migraines and a treatment rationale. The basis of my hypothesis is the fact that excitatory amino acid transporter (EAAT)-mediated cysteine transport via the cysteine/glutamate anti-porter is the mechanism used by neurons to obtain cysteine for the synthesis of reduced glutathione (GSH), a key molecule in preventing oxidative stress and neuronal toxicity. A key feature of my hypothesis is the observation that disruptions in glutathione homeostasis and alterations in glutathione-dependent enzyme activities appear to be associated with the induction and progression of several neurodegenerative diseases (5).
These transporters mediate cysteine entry in exchange for intracellular glutamate and conditions impacting this transporter affect the transport of cysteine into cells (6, 7). Maintaining sufficient intracellular concentrations of cysteine is critical not only for protein synthesis but also for maintenance of cellular redox homeostasis as cysteine is the rate limiting component for the synthesis of GSH, a critical co-factor of the intracellular antioxidant machinery (6, 7). Furthermore, low intracellular GSH leads to disruption of normal mitochondrial function (8) which impacts neuronal cellular energetics, a condition that has been linked to migraine headaches (9).
I hypothesize that migraine headaches are in part, a consequence of a deficit in neuronal intracellular reduced glutathione levels and that acute or chronic inhibition in the transport of cysteine via the EAAT transport system may be a primary event in the initiation and propagation of migraine headaches. I further hypothesize that exogenously supplied GSH directly to the trigeminal nerve and subsequently to the central nervous system via the trigeminal nerve pathway could restore the neuronal GSH by circumventing the EAAT transport system.
Unfortunately, supplying GSH exogenously to the CNS is problematic due to the extremely low bioavailability of oral GSH formulations and chemical instability of GSH nasal sprays or other liquid GSH formulations. To overcome these obstacles, I developed an orally delivered formulation containing GSH in a proprietary effervescing delivery system designed to transport directly GSH to the CNS via the trigeminal nerves.
To test this hypothesis, I developed a formulation containing GSH in a proprietary effervescing liquid delivery system. Administration of the formulation to human subjects experiencing moderate to severe migraine headaches proved to be highly effective in 100% of the subjects without any observable side effects with maximum relief occurring in 12.6 ± 6 minutes (n = 50) (Submitted for publication). These results support my hypothesis and demonstrate that GSH supplied orally via a proprietary effervescing delivery system, can resists degradation and cross the blood brain barrier intact, thereby restoring neuronal intracellular levels of GSH relevant to the genesis and propagation of migraine headaches.
1. Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol (2010) 30:107– 1910.1055/s-0030-1249220
2. Goldberg LD.. The cost of migraine and its treatment. Am J Manag Care (2005) 11:S62–7.
3. World Health Organization. Headache Disorders. Fact Sheet No 277 (2007)
4. Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. (2013) ;16(5):821-47.
5. Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases.
William M. Johnson, Amy L. Wilson-Delfosse, John. J. Mieyal
Nutrients. (2012) October; 4(10): 1399–1440.
6. Watts SD, Torres-Salazar D, Divito CB, Amara SG. Cysteine transport through excitatory amino acid transporter 3 (EAAT3). PLoS One. (2014) Oct 2;9(10):e109245.
7. Aoyama K, Nakaki T. Neuroprotective properties of the excitatory amino acid carrier 1 (EAAC1). Amino Acids (2013) 45: 133–142.
8. Marí M, Morales A, Colell A, García-Ruiz C, Fernández-Checa JC. Mitochondrial glutathione, a key survival antioxidant. Antioxid Redox Signal. (2009) Nov;11(11):2685-700.
9. DaSilva, A. F., Granziera, C., Tuch, D. S., Snyder, J., Vincent, M., and Hadjikhani, N. Interictal alterations of the trigeminal somatosensory pathway and periaqueductal gray matter in migraine. Neuroreport (2007) 4, 301–305.
10. Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. (2013) Mar;53(3):427-36.