By Paula M. Carnes
I have a confounding disease called chronic fatigue syndrome (CFS). Eight years ago I began a Don Quixote-like quest for effective treatment.
In the first year I found myself tilting at windmills, put on an antidepressant, told to take zinc, strapped to a tilt table, stuck with needles, told to quit eating tomatoes. Then a PCR blood test indicated a mycoplasma infection. I started seven years of antibiotics and improved a great deal, but was not cured.
That positive test for infection revealed that not all my battles were “jousting at windmills.” Some were an actual enemy. But progress was slow. I began to suspect that many cases of CFS had infectious causes. Was the infection still there? Were there several infections? Was the underlying cause an immune system gone haywire?
I jousted with the government for awhile, making my impassioned speeches at the CDC and NIH. Although I held my lance proudly, the windmill just kept turning. If government funded research was not the place to win the battle, where would I fight? Where could patients turn for help?
Biotechs are the wave of the future for medical research. Smart scientists, rather than working for a university, set out to build a company that will solve a medical problem and, along the way, make the scientist a millionaire. It’s the American way. One stock-trader wrote on a biotech message board, “I love the idea I might be a part of something good and that I get paid for it, for wishing the best.”
I began to search for companies with immune modulator products in research, working on the assumption that CFS is an immune system disorder, never mind the cause.
Nancy Klimas, M.D., has done research on CFS and the immune system which indicates a shift from Th1 immunity to Th2 in CFS patients. Klimas wrote the following:
“Based on the postulates of viral and autoimmune etiologies of CFS, several interventions have been designed and tested by different research groups around the world, including the United States, Sweden, United Kingdom, Italy, and Japan. This review addresses those interventions aimed at altering the balance of certain cytokines, the mediators of immune responses. Patients with CFS who show evidence of activation of the immune system have poor immune cell function and a predominance of what is called a T -helper (Th)2-type cytokine response when their lymphocytes are activated. A Th2-type response, which is characterized by production of cytokines such as interleukin (IL)-4, -5, and -10, favors the function of B lymphocytes, the cellular factories of immunoglobulins.
A predominance of a Th2-type response is therefore consistent with pathologies, such as autoimmunity and atopy, which are based on inappropriate production of immunoglobulins. Many of the CFS therapies discussed decrease the Th2-type predominance seen at baseline in CFS patients, thereby allowing a greater predominance of a Th1-type response, which favors the function of macrophages and natural killer cells.
The function of the latter cells, which have the natural ability of directly destroying invading microbes and cancer cells, is defective in untreated CFS patients. Typical Th1-type cytokines include IL-2 and interferon-gamma, and some of the therapies induce their production.”
Among the hundreds of small biotech firms I have investigated thus far, I found only a handful studying immune system modulators. It is not the “in” thing as most scientists are impressed with drugs carefully designed to target specific infections, cancers or genetic defects. This is not possible with CFS as the specific causes are unknown. In my search I discovered one company with a product already available in several countries and relatively close to approval in the United States.
SciClone Pharmaceuticals in San Mateo, California is researching an immune modulator, thymalfasin or thymosin alpha 1, commercially known as Zadaxin.
“ZADAXIN is a subcutaneously administered, synthetic preparation of a natural peptide, thymosin alpha 1, which among other positive actions enhances the body's Th1 immune response to viral infections (current clinical studies target hepatitis C and hepatitis B) and to certain cancers (current clinical studies target malignant melanoma and hepatocellular carcinoma). ZADAXIN promotes stem cell differentiation into helper T-cells and differentiation of those cells into the Th1 subset by increasing the production of cytokines such as IL-2 and gamma interferon and decreasing production of IL-4. In addition, studies suggest that ZADAXIN also increases the number and function of cytotoxic T-cells and natural killer cells.
What really caught my attention as I was reading about Zadaxin was the connection between what Nancy Klimas was saying about CFS patients’ immune system and the use of Zadaxin in just this sort of immune system dysfunction. SciClone’s website states:
“Disease-causing agents which circulate in the blood are usually quickly recognized as "foreign" by the body’s humoral, or antibody-based, immune component. By contrast, diseases such as hepatitis C, hepatitis B, certain cancers and HIV, require a predominantly cellular immune response. These chronic diseases remain the most resistant to therapeutic intervention and are at the frontier of current medical investigation.
The cellular immune response encompasses T-lymphocytes differentiated into T-helper cells of two types, referred to as "Th1" and "Th2" subsets. Studies have shown that Th1 cells are fundamental to the eradication of hepatitis C. Conversely, when T-cells are predominantly of the Th2 type, the hepatitis C virus is able to evade the body’s immune response and the disease becomes chronic. Thus, compounds which drive the immune response toward a Th1 profile could be highly effective in fighting chronic viral infection.”
When I heard that SciClone scientist, Cynthia Tuthill, Ph.D., Vice President of Scientific Affairs, would be presenting research at the TIDES 2003 conference on oligonucleotides and peptides I made a point to attend her lecture.
As the name “thymalfasin” suggests this drug is the peptide originally isolated from the thymus gland and tested on animals after the thymus gland was removed to reconstitute the immune system. A healthy functioning thymus is essential to a healthy immune system. Alternative medicine and anti-aging physicians have been prescribing thymus extract for some time. But this peptide is not readily absorbed through the gut, and there are some safely risks to the use of animal glandulars. Zadaxin, or thymalfasin, is a synthetic peptide which exactly matches the human thymosin alpha 1 peptide. It is taken by injection and has none of the risks of an animal product.
Zadaxin’s safety profile is outstanding. The SciClone website states, "ZADAXIN has been administered to more than 10,000 patients in both clinical and commercial use, alone and in combination with anti-viral and anti-cancer drugs, without producing any ZADAXIN related significant side effects or toxicities."
This product is also under study for vaccine enhancement and in treatment of cancer, namely melanoma. Indeed, one major problem in research is that Zadaxin would be useful in so many diseases it was difficult to figure out where to start. The company made some wise choices. One was to get market approval for Zadaxin in 28 foreign countries. At the same time focus in the United States was on hepatitis C, the predominant form of hepatitis in the U.S. SciClone tells us, "The trials are accruing 1,000 patients in over 40 sites throughout the U.S. and are multicenter, randomized, and double-blinded."
A fascinating outgrowth of this decision to market first in foreign countries has been that Zadaxin is already marketed in China and Hong Kong. During the SARS epidemic SciClone has made $15,000,000 in sales, enough to fund research through 2006. This is a huge accomplishment for a biotech firm, most small biotechs are millions of dollars in debt at any given time. Does Zadaxin cure SARS? There is no research to tell, but these sales will be used to push forward the research needed to give us the answers.
What does all this have to do with the CFS patient? Zadaxin is indicated in infections that shift the immune system to Th 2 when a Th 1 response is needed. Patients with CFS, fibromyalgia, and Gulf War Illness seem to have an immune system shifted toward Th 2 immunity. I spoke to Dr. Tuthill about this following her lecture. Her comment was that Zadaxin should be useful in any disease where the immune system needs to be shifted toward Th 1 immunity.
Klimas lists several possible reasons the immune system is out of kilter. Some of these reasons include infections such as viruses and certain bacteria which are intracellular such as Chlamydia, rickettsia , mycoplasma, and post Q fever syndrome. A combination protocol similar to the one being used in phase 3 trials for hepatitis C would include
either antivirals or antibiotics in combination with two injections of Zadaxin per week for six months to a year. This is not currently being tested, therefore a patient would need to assume responsibility for this treatment including the cost of purchasing Zadaxin in another country.
I currently own stock in this company. This is because I am convinced this company’s product will prove to be useful to many needy patients. I have put my money where my mouth is. May you succeed in health and wealth!