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By NCF Medical Committee
Copyright 2014

From Spring 2014 Forum

In 2011, a San Antonio news page reported on a very intriguing marker [1]. A bio-based company, known as Hyperion Biotechnology, had developed a saliva test for measuring fatigue. It sounded interesting to the NCF, so we did some checking and found several answers that appear to potentially link saliva fatigue markers to ionizing radiation exposure.

According to this news page, Hyperion has developed a simple test for measuring specific peptides in an individual's saliva to determine the level of fatigue. How did this company develop this technology? Here is where this gets very interesting. Hyperion does biomedical research for the military. In fact, Hyperion's Fatigue Biomarker Index, known as FBI, was developed through two Army grants totaling $875,000. According to the article, the Army wanted to improve the way it assessed fatigue in trainees. It took Hyperion five years to complete product development, which included tests involving about 500 people, mostly in the military, and 4,000 saliva samples.

Well, the NCF's research had identified additional information because of Hyperion's patent applications [2,3]. In the 2011 patent application, Hyperion's work was sponsored by both the US Army as well as the US Air Force. Two amino acid peptides are identified that represent the fatigue biomarkers used for testing. These peptides are part of the basic proline-rich protein genes known as PRB1 and PRB2. PRB1's gene product is known as Basic Salivary Proline-rich Protein 1 while PRB2's gene product is known as Basic Salivary Proline-rich Protein 2.

It turns out that Hyperion's FBI test results are a measure of physical performance capability and are used to predict success in Special Operations Forces members. As compared to controls, a decrease in the levels of FBI are indicative of excessive fatigue in normal people.

If we now fast forward a bit, Hyperion has completed work with the CDC and have published their results associated with the testing of CFS/ME patients [3,4]. In September 2012, Hyperion had won a Distinguished Abstracts Award for Chronic Fatigue Syndrome Research at the American Association for Clinical Chemistry (AACC) annual meeting. Their abstract was titled "Search for a novel salivary biomarker candidate for chronic fatigue syndrome."

As we look at the 2014 patent application, there are many interesting details here especially since it is all about CFS. First, a staggering 21,165 subjects were screened to determine inclusion/exclusion criteria! This was ultimately dwindled down to just 45 controls and 46 CFS patients! We would suggest that this effort was completed with the mighty help of the CDC since their name is on the AACC Annual Meeting abstract and because patient selection involved telephone screening methods typical of other CDC based CFS studies!

According to this document, "The present invention also provides a method of identifying a subject as having chronic fatigue syndrome or having an increased likelihood of having or developing chronic fatigue syndrome, comprising: a) measuring the amount of 1) human basic proline-rich protein 1 (PRB1), 2) human basic proline-rich protein 2 (PRB2), and 3) human basic proline-rich protein 4 (PRB4) in a biological sample from a test subject; and b) calculating the amount of the proteins relative to the total amount of protein in the sample of (a) to determine a biomarker index for the test subject, wherein a biomarker index of the test subject that is higher than a threshold biomarker index identifies the subject as having chronic fatigue syndrome or having an increased likelihood of having or developing chronic fatigue syndrome. "

Although the description above is just a short excerpt from the entire document, the key point is that these human basic proline-rich proteins (PRB1, PRB2 and/or PRB4), or their associated amino acid peptides, are used to identify not only normal fatigue in healthy subjects but also the likelihood of CFS in ill subjects.

To get to the point that we are trying to make here, according to the published medical literature, is that these proline-rich proteins are modulated by radiation effects [5,6]. In 2006, the NCF had published an article in The Forum that served to remind patients about some of the key characteristics from the Lake Tahoe outbreak as outlined in Hillary Johnson's book, Osler's Web [7]. Dr. Paul Cheney along with Dr. Dan Peterson had identified numerous B-cell lymphomas in the salivary or parotid glands in their CFS patients. These glands are very sensitive to radiation effects and this observation from the outbreak is in total agreement with the implications of Hyperion's research.

The salivary glands make as much as a quart of saliva each day. Saliva is important to lubricate your mouth, help with swallowing, protect your teeth against bacteria, and aid in the digestion of food. The three major pairs of salivary glands are (A) the parotid glands on the insides of the cheeks; (B) the submandibular glands at the floor of the mouth; and (C) the sublingual glands under the tongue. In addition, there are also several hundred minor salivary glands throughout the mouth and throat. Alterations to proline-rich proteins are associated with the development of dental problems, dry mouth, etc. Many patients are plagued with these problems.

  1. Your spit can tell you're tired; Pack W; My San Antonio; Nov 17, 2011;
  2. Methods and compositions for biomarkers of fatigue, fitness and physical performance capacity; US Patent Application #20110077472; Inventors: Kalns JE, Michael DJ; Assignee: Hyperion Biotechnology; Dated - March 31, 2011
  3. Methods and compositions for biomarkers of fatigue; US Patent Application # 2014002405; Inventors: Kalns JE, Michael DJ; Assignee: Hyperion Biotechnology; Dated - January 23, 2014
  4. Search for a novel salivary biomarker candidate for chronic fatigue syndrome; AACC Annual Meeting; Kalns J, Michael D, Whistler T, Valle B; 2012
  5. Does irradiation affect the protein composition of saliva; Hannig M, Dounis E, Henning T, Apitz N, Stösser L; Clin Oral Investig. 2006 Mar;10(1):61-5.
  6. Changes in protein composition of saliva from radiation-induced xerostomia patients and its effect on growth of oral streptococci; Cowman RA, Baron SS, Glassman AH, Davis ME, Strosberg AM; J Dent Res March 1983 62: 336-340.
  7. Connecting science to find the truth; NCF Medical Committee; The National Forum, Winter 2007

[Ed. Note: Dr. Whistler, whose name I’ve underlined in the references above, did a great deal of previous work with the late Dr. William Reeves from the CDC as well as with the CAA’s Dr. Suzanne Vernon and the three published over a dozen medical journal papers together. Hyperion, in 2011, offered their testing kit for “fatigue” by mail but that offer is no longer available and that kit can no longer be found on the internet.]

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