ABOUT MIGRANADE
Migranade, Inc. is a California based pharmaceutical company that discovers, develops and markets therapeutics for a variety of neurological conditions.

Dr. Charles B. Hensley (Migranade's Founder, Chairman and Chief Exectutive), is an internationally known innovator, visionary, entrepreneur and author with a global footprint. He has been featured in USA Today, Time Magazine and has appeared on CNBC Squawk Box Asia.

Dr. Hensley first rose to prominence in 1999 when he discovered the mechanism by which viruses infect and cause common colds. He later developed ZICAM Cold Remedy and founded ZICAM, LLC which marketed this iconic American brand that in now distributed in 88,000 retail stores.

In 2013, Dr. Hensley developed a revolutionary effervescent delivery system platform designed to effectively deliver active ingredients directly to the central nervous system (CNS).

Based on Dr. Hensley's discovery of the role of glutathione (GSH) in the genesis and propagation of mirgraine headaches, he has developed a treatment for migraine headaches using his delivery platform to rapidly supply GSH to the CNS. The product, MIGRANADE Migraine Relief, is market ready and is poised to be a blockbuster in the OTC pain relief category.

Dr. Hensley has assembled the best of the of the original ZICAM team in order to bring MIGRANADE Migraine Relief to the market. The Company is pursuing an agreement with the United States Armed Forces to include MIGRANADE Migraine Relief as an issuance to active military personnel.

The product will also be distributed nationally through the Company’s affiliate marketing program and in all the major big box retailers (Costco, Walmart, Walgreens, CVS, Rite Aid).









MANAGEMENT TEAM
Charles B. Hensley, Ph.D.
Founder, Chairman and Chief Executive Officer
Dr. Charles B. Hensley is an internationally known innovator, visionary, entrepreneur and author with a global footprint. He has been featured in USA Today, Time Magazine and has appeared on CNBC Squawk Box Asia. Dr. Hensley first rose to prominence in 1999 when he discovered the mechanism by which viruses infect and cause common colds, developed ZICAM Cold Remedy and founded ZICAM, LLC which marketed this iconic American brand that in now distributed in 88,000 retail stores.

In 2001, inspired by the threat of emerging viral disease, he developed "The Hensley Algorithm" which he used to pioneer the development of cocktails containing naturally occurring compounds as anti-viral therapeutics. Dr. Hensley discovered and developed the antiviral medicine, VIRA 38 (SARS, Influenza, Avian Influenza, Exotic Newcastle Disease and PARVO) and founded PRB Pharmaceuticals to bring the treatment to the international stage.

In 2003, the President of Taiwan requested Dr. Hensley to travel to Taipei to help his country find a solution to the SARS epidemic. Without hesitation, Dr. Hensley and his team went to Taipei and spent the duration of the epidemic there working with government and hospital officials. In 2005, at the government of Vietnam’s request, Dr. Hensley traveled to Hanoi to discuss strategies on how to curtail their avian influenza outbreaks. That same year, he traveled to Egypt to work on their avian influenza problem.

In 2008, Dr. Hensley developed TheraMax Cold and Flu and TheraMax Allergy which were successfully launched nation-wide into Big Box retail.

Dr. Hensley has written two novels, COLD WARS and VIRAL WINDS. COLD WARS is the story of his discoveries and the development and marketing of what many consider to be the “Cure for the Common Cold” (ZICAM). VIRAL WINDS is Dr. Hensley’s account of his scientific and political experiences with emerging viral disease such as SARS and Avian Influenza. In 2016, United Talent Agency signed on to package and distributed a feature film based on Dr. Hensley’s life story.

Dr. Hensley is a graduate of the University of Oklahoma and received his Ph.D. from the University of Southern California in Physiology and Biophysics. Hensley completed his post-doctoral fellowship at the University of Southern California School of Medicine where he specialized in the regulation of gene expression, molecular cardiology and drug development.

Shaman Bakshi
Chief Financial Officer and Chief Financial Officer
Shaman Bakshi has an extensive career in structured finance spanning more than 15 years. Mr. Bakshi has served as senior managing director at General Electric Capital Corporation, a leading financial institution in several business sectors with an expertise in Private Equity and Corporate Finance. In his five years at GE Capital, he was able to drive cost out of billion dollar businesses within the GE portfolio to the tune of $750 million and increased operating efficiency twelve fold.

For his work in managing several businesses within General Electric, Mr. Bakshi was tapped by Mr. Welch to lead several billion- dollar transactions within GE Healthcare in Europe, GE Aircraft Engines, GE Infrastructure, and Antares Capital Corporation acquisition for GE Capital. For the last nine years he has structured equity and senior/mezzanine debt for Private Equity Sponsors, Manufacturing, Retail, Gaming, Healthcare, Tech & Media, and Real Estate industries. All told he has led originations that have committed over $20BN in financing for GE Capital clients. He is a master developing and executing Corporate Finance Strategies to minimize the cost of funds and maximize the return on invested capital.

Mr. Bakshi graduated with an MBA in Finance from the Anderson School of Business at UCLA with Highest Distinction and Summa Cum Laude with an undergraduate degree in Finance and Economics from the University of Texas at Austin.


Ernesto Barron
Chief Scientific Officer
Mr. Barron career spans more than 30 years. He has managed the USC / Norris Cancer Center Cell and Tissue Imaging Core since it's inception in 1999, and has Supervised the Doheny Eye Institute Specialized Microscopy Core since 1995. Mr. Barron has extensive expertise in Transmission Electron Microscopy, Scanning Electron Microscopy, Laser Scanning Confocal Microscopy, Spinning Disk Confocal Microscopy, Laser Microcapture, Laser Microdissection, Live Cell Imaging, Light Microscopy, Fluorescence Microscopy, Tissue dissection and fixation, Digital Imaging and Computer Graphics. Mr. Barron has co-authored 28 publications, including the ground breaking paper on Zicam; Zinc nasal gel for the treatment of common cold symptoms: a double-blind, placebo-controlled trial. Hirt M1, Nobel S, Barron E., Ear Nos Throat J. 2000 Oct: 79(10).









SCIENTIFIC ADVISORY BOARD
Zeng Yi, M.D
Dr. Zeng Yi is the Dean of College of Life Science and Bioengineering, Beijing University of Technology. He is a graduate from Shanghai First Medical University and he is an Academician of Chinese Academy of Sciences, foreign member of France National Academy of Medical Sciences and Foreign member of Russian Academy of Medical Sciences. He is the former Director of the Institute of Virology, former President of Chinese Academy of Preventive Medicine and a member of the Executive Board of International Union of Microbiological Society (2000-2002). He has been the chief scientist of the National Center for Prevention and Control of AIDS, President of Chinese Foundation for Prevention of STD and AIDS, President of China Preventive Medicine Association, member of the WHO Expert Advisory Panel on Cancer, and member of the Steering Committee of the Asia Pacific Leadership Forum on HIV/AIDS and Development (APLF). He has recieved 25 awards from the National and Provincial governments and Ministry of Public Health, the Special Contribution Award for Young Scientists and the Tan Kah Kae Prize in medicine. He has published more than 500 papers in Chinese and in English.

Li Zelin, M.D.
Dr. Li Zelin is the Chief Professor of Department of Virology-Pharmacology at the College of Life Science and Bio-engineering. She was a WHO fellow member in London School of Hygiene and Tropical Medicine U.K and was selected as the member of Royal Society of Tropical Medicine and Hygiene. She was with The China Academy of Traditional Chinese Medicine for over 40 years as Chief Professor of the Department of Pharmacology at the Institute of Chinese Materia Medica. She has published 104 papers in Chinese and and in English.

Stephen P. Chen, M.D.
Dr. Chen obtained his Medical Degree from Harvard Medical School and served his residency at the University of Southern California. He is the recipient of many awards including the prestigious GlaxoSmithKline Pulmonary Fellowship Award. Dr. Chen has lectured for GlaxoSmithKline, Sepracor, Astra Zeneca, DEY Pharma, Astellas, Forrest, and Boehringer Ingelheim.
 Breaking News
January 2017

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
RAPID COMMUNICATION

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.




LITERATURE CITED

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.