History of the use of Growth Factors
“The fact is that GF’s have been used as far back as 18 years ago at UCLA. They used them to repair bones that wouldn’t heal. The first publication of GF use in the US was in 1982. In Europe it’s even older. Pope Pius XII received live cell injections on his death bed in 1952 and lived another four years. They’ve been out there for many, many years. But it’s only in the last ten years that we’ve figured out how these things work.”
“You don’t have to use human growth factors. You can use mammalian GF’s. They inaugurate stem cell differentiation. It will become whatever is needed. The stem cell will migrate to the site of injury and then begin to repair any injury. All you need is growth factors and sufficient growth hormone. This is very protein synthesis intensive.”
Two discoveries in the past year
(I commented that a year ago he was only exploring the use of bGF’s, and there was no mention of GH.) “I know. In the past year we’ve made two discoveries. Discovery one: CFIDS is a growth hormone deficiency syndrome. I didn’t know that last year. Discovery two was this article in Newsweek (May 22, 2000) that says the success or failure of stem cell repair depends on age.”
Growth Hormone decreases with age
“Young people with CFIDS, like teenagers, they tend to get through this nine times out of ten. But once you get past twenty, you’re lucky to see one out of ten get through this. Why? Growth hormone. You have to have enough GH to get through it. Young people still get hit, some very hard, but they have so much GH, they can loose 50% and still have enough. Once you reach 20, your GH is half what it was at 15. It precipitously drops after puberty. Ninety percent of CFIDS patients under 20 have enough GH to recover. I think that this syndrome transforms you into a very low GH state and once that happens, you can’t really repair the damage. You can get through the syndrome, maybe; get through the pathophysiology of the disease, maybe; but then you’re locked in, you’re limited. So, to repair the damage – and the focus of that damage is the hypothalamus – you need GH. And since GH seems to be the center of aging, essentially the treatment of Phase III CFIDS is going to mimic the treatment of age-related injury.”
Repairing the damage (from GH deficiency)
“So the real issue behind all this is, . . . what I’m really interested in is not simply giving you GH because you’re GH deficient, although that may be justification in itself. My real interest is to follow the GH with bGF’s to repair the damage from which the GH deficiency comes. Taking GH and bGF’s could restore GH and repair the other damage. Pretty amazing stuff. We have fifteen patients poised to take this. It’s a pretty elaborate protocol, and involves taking one month of GH alone, to get the dose adjusted for each individually.” (They continue the GH throughout the six-month study.) “Then they go on mesenchyme for five months, then liver for one month, then thymus for one month, adrenal for one month, and brain for one month. Those are growth factors taken from those organ systems.”
[A few weeks back, some asked if it would be possible to obtain a copy of Dr. Cheney’s 16-page protocol for his recombinant human Growth Hormone (rhGH) and bovine Growth Factor (bGF) study. Cheney’s not comfortable with the full protocol being in circulation at this time.] He said “There are aspects of the study that we are testing and unsure of the outcome. I fear some might launch therapies based on the protocol which would be unadvisable. What I think might be alright (to share) is the first few pages which outline the conceptual framework and supportive literature.”
The following are excerpts taken from the 16-page study protocol:
The purpose of this open label study is to evaluate the efficacy of combined recombinant human growth hormone (rhGH) and bovine source growth factors (bGF’s) in the treatment of chronic fatigue syndrome (CFS) patients in various stages of illness. Previous clinical observations in CFS suggest that, individually, both rhGH and bGF therapies may lessen the severity of certain symptoms of CFS and improve functionality. The combination of GH and bGF’s is likely to be very synergistic in CFS given the evidence of growth hormone deficiency reported in CFS patients. The treatment may be particularly helpful to late stage (phase III) patients who are symptomatically improved but physically limited and some middle stage (phase II) patients who are treatment resistant. The study is an ambitions but promising attempt to stimulate the body’s innate healing potential to repair damage done to it over many years of CFS related pathology.
Safety and Rationale for Using Human Growth Hormone:
Recombinant human growth hormone (rhGH) is FDA approved for short stature children and adults deficient in growth hormone. (1) It is also used for AIDS wasting syndromes. RhGH is contra-indicated in patients with active cancer though some argue it could help prevent cancer. There is no evidence that GH causes cancer. The highest levels are adolescence and the lowest levels are in the elderly as GH declines with age. The most common side effects of rhGH therapy are arthralgias, expanded plasma volume and edema. recent studies in CFS patients have shown that they are growth hormone (GH) deficient documented by insulin tolerance tests and by Q15 minute overnight sampling of GH.(2) Growth hormone is essential for protein synthesis, hormone action (especially thyroid and sex hormones), post exercise recovery and may be critical to the healing process itself, especially after severe physiologic injury. GH deficiency may masquerade as osteoporosis, lipid disorders, wasting syndromes, menopausal syndrome, PMS, depression, cognitive dysfunction and obesity. GH is synthesized in the anterior pituitary gland primarily under the control of the hypothalamus. It slowly declines with age and has been identified as critical to the aging process. In CFS patients, rhGH appears to be very bioactive. However, CFS patients are ver sensitive to it with fatigue exacerbation when using typical doses. Exceptionally small doses, on the other hand, appear to quickly bring benefits in energy and improved organ function, especially liver and immune function. Over time, the benefits slowly build and include functional improvements.(2) The issue of active cancer can be address by modest cancer screening exams such as pap smears and mammography for women, PSA for men, colon cancer screens and watching for skin changes. These can be accomplished by primary care physicians, as appropriate for each patient, before the study begins. In addition, patients can use blood testing for cancer markers such as the AMAS test to screen for many cancers.
Safety and Rationale for Using Bovine Growth Factors:
The low molecular weight bovine growth factor products (bGF’s) are derived from carefully selected bovine stock and are manufactured to assure the safety of these products. A reputable Canadian biotechnology company (Atrium) manufactures them in Quebec, Canada. No case of bovine sponiform encephalopathy of BSE (mad-cow disease) has ever been reported in Canadian stock. Similar “live cell” products have been used as injections in Europe for over seventy years in health spas as rejuvenation therapy and by physicians for the treatment of chronic disease.(3) Pope Pius XII received live cell injections on his death bed by the leading Swiss proponent at that time, Dr. Paul Niehans, and lived another four years.(4) There is over a half century long history of their safe use in humans. In the U.S., this type of therapy was first legitimized in 1981 with the publication of a 59% remission rate of an immunosuppressive disease of childhood in the New England Journal of Medicine using intramuscular injections of thymus extract from 5-day-old calves.(5) Kutapressin is a similar product in many ways to liver-fbGF except that it has only four, bioactive low molecular weight protein extracts from adult pig liver. Kutapressin has been used safely since 1938 as an injection for inflammatory skin disorders and has been used safely and effectively in CFS patients for over ten years.(6)
Low molecular weight growth factors from human bone cell cultures have been used as implants to successfully heal nonunion bone fractures at UCLA as far back as 1982.(7) More recently, implanted human fetal brain tissue(8) as well as cultured human stem cell transplants(9) have been used to successfully treat younger (though interestingly not older) patients with Parkinson’s disease. Other studies have shown that donor embryonic cells need not be human to work.(10) Finally, it has been shown that injected low molecular weight growth factors alone can induce functional recovery from Parkinson’s-like syndromes induced by drugs in monkeys.(11) These treatment trials were guided by the same principles of healing used to design this treatment protocol. One significant difference is the addition of growth hormone (GH) to our therapy design since CFS patients are deficient in GH. Such a deficiency would be expected to render the bGF’s significantly less effective, which might explain the lack of success of this type of treatment in older Parkinsonian patients. The large age related differences in GH might also explain the much better long-term prognosis of CFS teenagers vs. the poor prognosis of their adult counterparts with CFS. The addition of GH is expected, therefore, to significantly increase the bGF’s healing potential as orchestrators of endogenous stem cell migration, differentiation and integration to effect tissue healing. The target tissues for healing in this study are liver, immune system, adrenal gland, brain and especially the hypothalamus.
(1) Salomon F. Cuneo RC, Hesp R et al., “The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency”. N. Eng J. of Med., 1989; 321: 1797-1803
(2) Moorkens, Greta, “Endocrine and Metabolic Aspects of the Chronic Fatigue Syndrome”, PhD Thesis May 2000, Antwerp University, Belgium
(3) Niehans, Paul, Introduction to Cellular Therapy NY: Coopers Square Publ., 1960
(4) Culbert, ML in Live Cell Therapy for the 21st Century Chula Vista, CA: The Robert W. Bradford Foundation – PUbl., 1993
(5) Osmond ME, et al, “Demonstration of abnormal immunity, T-cell histamine H-2 receptor deficiency, and successful therapy with thymic extract” N. Eng. J. Med., Jan 15, 1981
(6) Steinbach, T., Hermann, W., Lawyer, C., Montefiore, D., Wagle, S., Gawish, A., and Ferguson, D., “Subjective reduction in symptoms following long term treatment with a porcine liver extract (Kutapressin): a phase I trial”, Clin. Inf. Dis. 1994; volume 18, Suppl I: S114
(7) Demers C, Hamdy R “Bone morphogenic proteins” Science & Medicine Nov/Dec 1999; vol 6, No 6: 8-17
(8) Lindvall O, Brundin P, Widner H “Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease” Science 1990; 247: 574-577
(9) Cowley, G. “The new war on Parkinson’s disease” Newsweek 2000; 22 May issue: 52-58
(10) Isacson O, Deacon T, Pakzaban P, Galpern WR, Dinsmore J and Burns LH. “Transplanted exogenic neural cells in neurodegenerative disease models exhibit remarkable azonal target specificity and distinct growth patterns of glial and azonal fibers” Nature Medicine 1995;1: 1189-1194
(11) Gash DM and eleven others “Functional recovery in Parkinsonian monkeys treated with GDNF” Nature 1996; 380: 252-255
CLARIFICATION ON CHENEY’S WORK WITH GROWTH HORMONE AND GROWTH FACTORS:
Dr. Cheney is refining the use of growth hormone and growth factors for use in CFIDS. Others have been researching this area for years. In particular, Dr. Sam Baxas pioneered the use of human growth hormone and growth factors more than twenty years ago. A discussion of his work can be found in the book “Grow Young with hGH” by Ronald Klatz.