Naltrexone: Sufferer joins in battle for trials of 'wonder drug'

[Rich66]

Sufferer joins in battle for trials of 'wonder drug'

Tuesday, July 21, 2009, 12:01
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A LLANELLI man is spearheading a fight for trials to be carried out on a "wonder drug" which could help treat people with illnesses ranging from Aids to cancer.
Multiple sclerosis sufferer Andrew Barnett, of Llangennech, and his partner, Jayne Crocker, who has ulcerative colitis, both take a drug called Naltrexone.
The pair say the generic drug has been used with remarkable success to treat their conditions, and are now calling on the Government to help make it available to all.
However, the Assembly says it will only consider medicines appropriately licensed by the Medicines and Healthcare Products Regulatory Agency.
The drug went out of patent in 1986. It was introduced into the UK by Swansea-based physician Bob Lawrence in 2000.


The drug works by blocking endorphin receptors for a limited period of time, which then boosts them five-fold.
This stimulates the immune system to produce cells that repair the body.
Only about 200 doctors in the country currently prescribe the drug — many more are reluctant to do so, because it has not yet been approved by health chiefs.
Mr Barnett described how last year he reached a point where he could only support his weight on crutches. The 49-year-old was crawling out of the front door to get to his car, dragging his legs behind him.
But after taking the drug, there was a remarkable improvement.
Mr Barnett said: "Within four days of taking Low Dose Naltrexone (LDN), I could walk to the car with two walking sticks, and even walked down a friend's country path to visit them.
"The downward spiral ended there, in fact I seem to be improving as time goes by."
His partner Jayne, from Milford Haven, decided to use LDN for ulcerative colitis, which she has had for 25 years.
"Within the first month I was no longer in pain," she said.
"It's not a miracle drug, but it does work for a lot of people."
They say as well as being effective, the drug is cheap, costing less than £1 a day, and could save the NHS vast sums of money.
The couple have created a petition to take their fight to 10 Downing Street, and have already gathered around 3,000 signatures.
Mr Barnett, who has secondary progressive MS, said: "We urge the Government to fund a trial of LDN on the NHS.
"Because of lack of interest by drug companies, without political intervention, we will probably never see this drug trialled."
An Assembly spokesman said the National Institute for Health and Clinical Excellence had looked at the drug.
He continued: "Since there is no licensed product available for low dose administration in the UK it can only be obtained under a special manufacturing licence.
"Products of this nature are obtained on the full clinical responsibility of the prescriber, and any liability for any harmful effects caused rests with them."
He said researchers with an interest in Low Dose Naltrexone could apply for funding for specific research.
*To find out more about LDN and the petition, visit www.ldnnow.co.uk

[Rich66]

The Long-term Survival of a Patient With Pancreatic Cancer With Metastases to the Liver After Treatment With the Intravenous -Lipoic Acid/Low-Dose Naltrexone Protocol

Burton M. Berkson Integrative Medical Center of New Mexico and New Mexico State University, Las Cruces
Daniel M. Rubin
Scottsdale, Arizona, rubin@rubinmedical.com
Arthur J. Berkson
Department of Family Practice, University of Illinois at Chicago, Illinois Masonic Medical Center, and the Department of Family Practice, Advocate Health Center, Chicago, Illinois
The authors describe the long-term survival of a patient with pancreatic cancer without any toxic adverse effects. The treatment regimen includes the intravenous -lipoic acid and low-dose naltrexone (ALA-N) protocol and a healthy lifestyle program. The patient was told by a reputable university oncology center in October 2002 that there was little hope for his survival. Today, January 2006, however, he is back at work, free from symptoms, and without appreciable progression of his malignancy. The integrative protocol described in this article may have the possibility of extending the life of a patient who would be customarily considered to be terminal. The authors believe that life scientists will one day develop a cure for metastatic pancreatic cancer, perhaps via gene therapy or another biological platform. But until such protocols come to market, the ALA-N protocol should be studied and considered, given its lack of toxicity at levels reported. Several other patients are on this treatment protocol and appear to be doing well at this time.

Key Words: pancreatic cancer • naltrexone • lipoic acid • survival


Integrative Cancer Therapies, Vol. 5, No. 1, 83-89 (2006)
DOI: 10.1177/1534735405285901


Integr Cancer Ther. 2009 Dec;8(4):416-22.
Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases.

Berkson BM, Rubin DM, Berkson AJ.
The Integrative Medical Center of New Mexico, Las Cruces, NM, USA.
The authors, in a previous article, described the long-term survival of a man with pancreatic cancer and metastases to the liver, treated with intravenous alpha-lipoic acid and oral low-dose naltrexone (ALA/N) without any adverse effects. He is alive and well 78 months after initial presentation. Three additional pancreatic cancer case studies are presented in this article. At the time of this writing, the first patient, GB, is alive and well 39 months after presenting with adenocarcinoma of the pancreas with metastases to the liver. The second patient, JK, who presented to the clinic with the same diagnosis was treated with the ALA/N protocol and after 5 months of therapy, PET scan demonstrated no evidence of disease. The third patient, RC, in addition to his pancreatic cancer with liver and retroperitoneal metastases, has a history of B-cell lymphoma and prostate adenocarcinoma. After 4 months of the ALA/N protocol his PET scan demonstrated no signs of cancer. In this article, the authors discuss the poly activity of ALA: as an agent that reduces oxidative stress, its ability to stabilize NF(k)B, its ability to stimulate pro-oxidant apoptosic activity, and its discriminative ability to discourage the proliferation of malignant cells. In addition, the ability of low dose naltrexone to modulate an endogenous immune response is discussed. This is the second article published on the ALA/N protocol and the authors believe the protocol warrants clinical trial.

PMID: 20042414 [PubMed - in process]


Here is the video from the LDN Conference regarding pancreatic cancer:
http://www.youtube.com/watch?v=xy65UGsVMac

1: Anticancer Res. 2009 Aug;29(8):2927-32. Links

Methylnaltrexone, a peripherally acting opioid receptor antagonist, enhances tumoricidal effects of 5-Fu on human carcinoma cells.

Wang CZ, Li XL, Sun S, Xie JT, Aung HH, Tong R, McEntee E, Yuan CS.
Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.
BACKGROUND: Methylnaltrexone, a novel peripherally acting opioid receptor antagonist, is used to treat opiate-induced constipation in cancer patients. Its effects on the activities of chemotherapeutic agents, however, have not been evaluated. In this study, the effect of methylnaltrexone on the action of 5-fluorouracil (5-FU) was tested in three human cancer cell lines. MATERIALS AND METHODS: Treatment was for 72 h and the effects on cell proliferation were measured in human SW-480 colorectal cancer cells, MCF-7 breast cancer cells and non-small cell lung cancer cells in vitro. The apoptotic effect was analyzed by using flow cytometry. The cell cycle and expression of cyclin A were assayed after staining with propidium iodide and cyclin A-fluorescein isothiocyanate. RESULTS: 5-FU decreased the cancer cell growth significantly in all three cancer cell lines in a concentration-dependent manner and methylnaltrexone enhanced the actions of 5-FU. Compared to 5-FU 10 muM alone on SW-480 cells (63.5+/-1.1%), on MCF-7 cells (58.3+/-3.1%), or on non-small cell lung cancer cells (81.3+/-1.6%), 5-FU 10 muM plus methylnaltrexone 1.0 muM reduced cancer cell growth in all three cell lines to 50.2+/-2.9% for SW-480 cells (p<0.05), 50.0+/-1.7% for MCF-7 cells (p<0.05) and 68.7+/-2.2% for lung cancer cells (p<0.01). Methylnaltrexone alone also showed anti-proliferative activity in the three cell lines. Methylnaltrexone at 1.0 muM, reduced SW-480 cell growth to 81.9+/-3.7% (p<0.01), MCF-7 cell growth to 85.9+/-2.4% (p<0.01) and lung cancer cell growth to 85.5+/-2.2% (p<0.01). Apoptosis was not induced by treatment of SW-480 cells with 1.0 or 10 muM methylnaltrexone for 48 h. However, methylnaltrexone increased the number of cells in the G(1)-phase and decreased the expression of cyclin A. CONCLUSION: At its therapeutic concentrations for opioid-induced constipation, methylnaltrexone does not attenuate and in fact may enhance the tumoricidal activity of 5-FU. Enhanced 5-FU activity may be attributed to the distinct pathways of 5-FU and methylnaltrexone, an effect that could give methylnaltrexone a complementary role in the treatment of cancer with chemotherapeutic agents.
PMID: 19661297

Mol Cancer Ther. 2008 Jun;7(6):1669-79.
Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor-induced angiogenesis.

Singleton PA, Garcia JG, Moss J.
Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Many patients with cancer receive combinations of drug treatments that include 5-fluorouracil (5-FU) and bevacizumab. Therapeutic doses of 5-FU are often associated with unwanted side effects, and bevacizumab is costly. Therefore, we explored potential agents that can reduce the therapeutic concentration of these drugs. Our data indicate that methylnaltrexone (MNTX), a peripheral antagonist of the mu-opioid receptor, exerts a synergistic effect with 5-FU and bevacizumab on inhibition of vascular endothelial growth factor (VEGF)-induced human pulmonary microvascular endothelial cell (EC) proliferation and migration, two key components in cancer-associated angiogenesis. MNTX inhibited EC proliferation with an IC(50) of approximately 100 nmol/L. Adding 100 nmol/L MNTX to EC shifted the IC(50) of 5-FU from approximately 5 micromol/L to approximately 7 nmol/L. Further, adding 50 ng/mL MNTX shifted the IC(50) of bevacizumab on inhibition of EC migration from approximately 25 to approximately 6 ng/mL. These synergistic effects were not observed with naltrexone, a tertiary mu-opioid receptor antagonist. On a mechanistic level, we observed that treatment of human EC with MNTX, but not naltrexone, increased receptor protein tyrosine phosphatase mu activity, which was independent of mu-opioid receptor expression. Silencing receptor protein tyrosine phosphatase mu expression (small interfering RNA) in human EC inhibited both synergy between MNTX and bevacizumab or 5-FU and increased VEGF-induced tyrosine phosphorylation of Src and p190 RhoGAP with enhanced activation of Akt and the actin cytoskeletal regulatory protein, RhoA, whereas silencing Src, Akt, or RhoA blocked VEGF-induced angiogenic events. Therefore, addition of MNTX could potentially lower the therapeutic doses of 5-FU and bevacizumab, which could improve index.

PMID: 18566238 [PubMed - indexed for MEDLINE]

[Rich66]

Cancer treatment triggers body's immune system

By Dr. Melanie Bone
DrBonesCancerComforts.org
Special to The Palm Beach Post
Thursday, February 07, 2008
Again I am thrilled to report that a reader introduced me to a new cancer treatment: Low-Dose Naltrexone, or LDN for short.
In 1984 the Food and Drug Administration approved the drug Naltrexone. It is a drug that blocks receptors for opiod narcotics - whether produced inside the body or given from an outside source.

What is an opiod narcotic, you ask? Opiod narcotics are the active ingredient in codeine, morphine, hydrocodone, oxycodone and heroin. They are known to attach to receptors in your brain that result in the "high" feeling that makes them excellent for pain management. The patient on opiods might still be able to feel the pain, but it does not bother them as much. Internal opiods are produced in our bodies (in the pituitary and adrenal glands, for example), and we call them endorphins and metenkephalins. Their production is increased by exercise, which is why that great feeling you get after a run or work-out is called a "high." Naltrexone was introduced as an antidote for someone who is accidentally given or takes too much of an opiod. A good example is in obstetrics. If the mother is given narcotic pain medication during labor and the baby is born a bit sleepy, a tiny amount of Naltrexone is given to reverse the effects of narcotics transferred through the umbilical cord. Likewise, street addicts found comatose are given the drug to "awaken" them from an overdose. So how does a drug that interferes with opiods affect cancer? A psychiatrist in New York, Dr. Bernard Behari, determined that our immune system is sensitive to our internal opiods. During our normal sleep-wake cycle, there are periods when our internal opiods, the endorphins and metenkephalins, are at higher levels. He found that by giving patients tiny doses of Naltrexone, he "fooled" the brain into thinking that there were not enough opiods available, which led to increased internal opiod production. By "up-regulating" the system, especially between 2 a.m. and 4 a.m., he was able to get the immune system to work better. At first Dr. Behari worked with HIV patients. Later, he transferred his study to the cancer arena. His work was pioneering. Now there is complete acceptance of the role that the immune system plays in identifying and killing cancer cells. It is associated with an increase in the "natural killer" cell population, which is a powerful branch of our immune system that may not work right in some cancer patients. LDN works in other ways, too. The endorphins it induces act directly on certain tumor cells, leading to a spontaneous "apoptosis" or early cell death. The metenkephalins it induces attach to opiod receptors on tumor cells and causes an "anti-growth" phenomenon. There are many Web sites devoted to LDN with links to the science behind it. I suggest LDNinfo.org or wikipedia. By no means is LDN designed to be a one-drug-fits-all panacea. But it may be valuable in the oncologist's tool kit to use either in conjunction with other drugs or when most others have failed. http://www.palmbeachpost.com/health/..._col_0207.html

[Rich66]

Low-dose naltrexone for disease prevention and quality of life
http://www.opioids.com/naltrexone/lowdosenaltrexone.pdf
Norman Brown a,*, Jaak Panksepp b
a Department of Humanities and Social Sciences, Embry-Riddle Aeronautical University, Daytona Beach, FL 32114, United States
b Department of VCAPP, College of Veterinary Medicine, Washington State University, P.O. Box 646520, Pullman, WA 99164-6520, United States
a r t i c l e i n f o
Article history:
Received 3 June 2008
Accepted 12 June 2008
s u m m a r y
The use of low-dose naltrexone (LDN) for the treatment and prophylaxis of various bodily disorders is
discussed. Accumulating evidence suggests that LDN can promote health supporting immune-modulation
which may reduce various oncogenic and inflammatory autoimmune processes. Since LDN can
upregulate endogenous opioid activity, it may also have a role in promoting stress resilience, exercise,
social bonding, and emotional well-being, as well as amelioration of psychiatric problems such a autism
and depression. It is proposed that LDN can be used effectively as a buffer for a large variety of bodily and
mental ailments through its ability to beneficially modulate both the immune system and the brain neurochemistries
that regulate positive affect.
 2008 Published by Elsevier Ltd.

[Rich66]

Updated:
See beginning of thread with new Berkson pancreatic info: abstract, video

[Laurel]

Rich,

You seem to have forgotten the link. BTW, have you ever looked into having Naltrexone for you mother? You can get this from a M.D. who specializes in naturopathy. I had it suggested to me when I was first dx'd, but I declined. Might revisit it. Hmmmm....

[Wyatt]

A LLANELLI man is spearheading a fight for trials to be carried out on a "wonder drug" which could help treat people with illnesses ranging from Aids to cancer.
Multiple sclerosis sufferer Andrew Barnett, of Llangennech, and his partner, Jayne Crocker, who has ulcerative colitis, both take a drug called Naltrexone.
The pair say the generic drug has been used with remarkable success to treat their conditions, and are now calling on the Government to help make it available to all.