Low Dose Naltrexone shows promise in Multiple Sclerosis animal study

[squiffy2]

http://www.msrc.co.uk/images/gallery/img_ldn.jpg

Another noninjectable drug that probably is already being overused against MS has shown promise in an animal study, researchers at Pennsylvania State University reported at the WCTRIMS. It is naltrexone, developed for treatment of drug abuse.

"Thousands of people are taking this drug for MS on the basis of what other people have said," said Dr. Ian S. Zagon, distinguished university professor in neural and behavioral sciences at Penn State. "So, we decided to do animal studies about its efficacy..................."

For the full report please go to MSRC: MS Research News : Drugs : Low Dose Naltrexone - Latest News (http://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=1306)

[lady_express_44]

For some reason this link isn't working for me right now, so I can't read what it said . . . but it's good to know they seem to have found a sample of mice that actually might resemble us humans who've tried LDN and can attest to it. :) :p

Cherie

[agate]

Here's the article. The last two paragraphs are about LDN.


Red Wine Molecule Might Battle MS

Other promising therapies reported at meeting in Montreal

Posted September 19, 2008

By Ed Edelson
HealthDay Reporter
FRIDAY, Sept. 19 (HealthDay News) -- Resveratrol, the compound in red wine that previous research has linked to longevity, has shown promise in an animal model of multiple sclerosis.

Mice with the MS-like condition called Wallerian degeneration slow (WldS) showed an initial weight gain when given resveratrol, researchers at the University of Utah reported Thursday at the World Congress on Treatment and Research in Multiple Sclerosis, in Montreal.

The weight gain occurred in the first two weeks of treatment. A microscopic study of nerve cell tissue at five weeks did not show any positive effect.

"They didn't look at the tissue under the microscope in the first two weeks," said Dr. John Richert, executive vice president for the research and clinical program of the Multiple Sclerosis Society. "Obviously, lots of things can make animals gain weight."

But weight gain of any kind is an encouraging sign in MS treatment, Richert said. "In inflammatory animal models of MS, one of the tell-tale clinical signs of the disease is weight loss. Weight loss often goes hand in hand with loss of neurological function."

The study "poses some questions," Richert said. "Obviously, a lot more needs to be done to see if the weight gain shows a beneficial effect on the disease process. This is evidence that it should be studied further."

Another report at the meeting was on positive results of a human trial of a new drug, laquinimod, which is given in pill form. Developed in the United States, it acts to prevent the body's immune system from attacking nerve cells.

An international study led by Italian physicians had two different doses of laquinimod given to 376 people with MS. "The higher dose was quite effective in reducing the lesions which characterize multiple sclerosis," said study author Dr. Giancarlo Comi, a professor of neurology at the University Vita-Salute and Scientific Institute San Raffaele, in Milan.

The higher dose reduced brain lesions by about 50 percent, Comi said. The people who got it also had a 30 percent reduction in MS flare-ups, which can cause vision loss and lack of coordination severe enough to prevent someone from walking, he said.

There will be a larger study that will recruit more than 1,000 people with MS and will last for two years, Comi said. If all goes well, it could be available for clinical use in three years.

A great advantage of the drug is that it can be taken by mouth, Comi said. "All the available therapies are injectable," he said. "Can you imagine how large an advantage this therapy would be?"

Another noninjectable drug that probably is already being overused against MS has shown promise in an animal study, researchers at Pennsylvania State University reported at the same meeting. It is naltrexone, developed for treatment of drug abuse.
"Thousands of people are taking this drug for MS on the basis of what other people have said," said Dr. Ian S. Zagon, distinguished university professor in neural and behavioral sciences at Penn State. "So, we decided to do animal studies about its efficacy."

The study of animals with an MS-like condition found that low-dose naltrexone helped, but high doses worsened the disease, Zagon said. Penn State is organizing a human trial of low-dose naltrexone in MS, he said. Meanwhile, use of the drug for the condition is not recommended, Zagon said.

[lady_express_44]

Here's the article. The last two paragraphs are about LDN.

Another noninjectable drug that probably is already being overused against MS has shown promise in an animal study, researchers at Pennsylvania State University reported at the same meeting. It is naltrexone, developed for treatment of drug abuse.

"Thousands of people are taking this drug for MS on the basis of what other people have said," said Dr. Ian S. Zagon, distinguished university professor in neural and behavioral sciences at Penn State. "So, we decided to do animal studies about its efficacy."

The study of animals with an MS-like condition found that low-dose naltrexone helped, but high doses worsened the disease, Zagon said. Penn State is organizing a human trial of low-dose naltrexone in MS, he said. Meanwhile, use of the drug for the condition is not recommended, Zagon said.



Thanks Agate. Later when I went to the wine link (from the other thread), I got access to this article, but couldn't on the link here. :confused:

Funny the words the use to describe it; "drug that probably is already being overused" and "thousands of people are taking this drug for MS on the basis of what other people have said." It sounds so naughty. :o

Maybe we are taking it simply because it is working for us, as well as for those people who are following behind us . . . :)

Cherie

[Annie123]

Cherie, the comments that draw my attention are:

"Meanwhile, use of the drug for the condition is not recommended, Zagon said."

I don't know if I've ever heard such a strong condemnation against using LDN. "...but high doses (of naltrexone) worsened the disease." Nothing is as simple as it first seems.

I wonder if this is the first scientific study showing such a negative effect? I'd want to know the demarcation line between low and high dose naltrexone if I was using this drug.

Best of luck LDN users.

[lady_express_44]

Cherie, the comments that draw my attention are:

"Meanwhile, use of the drug for the condition is not recommended, Zagon said."

I don't know if I've ever heard such a strong condemnation against using LDN. "...but high doses (of naltrexone) worsened the disease." Nothing is as simple as it first seems.

I wonder if this is the first scientific study showing such a negative effect? I'd want to know the demarcation line between low and high dose naltrexone if I was using this drug.

Best of luck LDN users.

That's the silly part . . . no one uses high-dose Naltrexone for MS anyway. :cool:

Naltrexone has undergone trials (for the diseases it's approved for) at dosages of up to 300 mg per day. It is usually rx'd at between 50 mg and 150 mg (MAX) for drug and alcohol addition.

People taking it for MS are using between 3.0 mg and 4.5 mg, which apparently proved helpful for mice in that study. It was the high dosage (which we don't use) that worsened the disease.

That's ok ... I don't think anyone has suggested that we might want to move up anyway.

Cherie

[Matthew's Mom]

That's ok ... I don't think anyone has suggested that we might want to move up anyway:):D

Yup, staying at my 3.0 and very happy with it.

Pam

[lady_express_44]

So I wanted to find out more about this “Zagon” dude, who seemed to be saying that he doesn’t recommend LDN for MS. What I found is he is actually a huge supporter for the use of LDN for many illnesses, and he has been studying the use of Naltrexone for about 25 yrs.

In one reference I found, he said the following:

“Multiple sclerosis (MS) is a devastating disease that affects over 400,000 individuals in the U.S. Knowledge about the origin of this disease, the course of MS, and treatment for MS needs to be elucidated. Our laboratory discovered that endogenous opioids are not only neurotransmitters, but also growth factors that regulate homeostasis, immunity, wound healing, and cellular renewal. Persistent opioid receptor blockade with the potent opioid antagonist naltrexone (NTX) stimulates these processes (e.g., cell proliferation, wound healing), whereas an intermittent daily opioid receptor blockade (low dose of naltrexone, LDN) is inhibitory and restores homeostatic processes.

LDN is in phase II trials for treatment of active Crohn's disease, and has proved highly successful. One endogenous opioid, methionine enkephalin (termed opioid growth factor, OGF), and its receptor, OGFr, have been identified to play a vital role in growth regulation, serving as a tonically active system that maintains cellular homeostasis and targets the cyclin-dependent inhibitory kinase pathway. OGF is currently in Phase II trials as a treatment for pancreatic cancer.

This research project raises the question of whether endogenous opioids and opioid receptors influence the course of MS. This is a novel and innovative concept that is valuable to explore. To test this hypothesis, we will subject rats to experimental autoimmune encephalomylitis (EAE), a model that mimics MS. Animals will be treated daily with a high dose of NTX (HDN) or a low dose of NTX (LDN). NTX produces a compensatory increase in native opioids and opioid receptors during receptor blockade. While HDN prevents opioid-receptor interaction the entire day, LDN lasts for 6-8 hr/day, and a supersensitive reaction occurs when NTX is no longer present (16-18 hr/day). In addition to daily body weights and EAE clinical scores, as well as weekly assessment of immune response, outcome measures will be qualitatively and quantitatively (with rigorous statistical analysis) evaluated on days 10 (onset), 20 (remission) and 40 (relapse) for inflammatory index, demyelination, apoptosis, weights and lengths of spleen and thymus, and neuronal pathology.

Our expectations are that continuous opioid receptor blockade will exacerbate the progression of MS, whereas a low dose of naltrexone will retard the course of this disease. Evidence for the involvement of endogenous opioids and opioid receptors in MS will open a new field of research related to the pathogenesis of this disease, and contribute to the development of strategies for treatment.”

This is a copy of what Dr. Ian S. Zagon wrote to Mary A. Boyle Bradley, author of Up a Creek, with a Paddle, LDN:

“LDN" is a misnomer. When we discovered the effects of opioid antagonists such as naltrexone and naloxone in 1979, this was purely happenstance. Around 1975, we were interested in the effects of exogenous opioids (opiates) (heroin, methadone, morphine) on children who were born to mothers that were addicted. The scientific literature revealed that these babies and children had neurological difficulties and were lower in body weight.

We (myself and Dr. Patricia McLaughlin) developed a model to look at this in animals. Along the way, I was doing another project on neuroblastoma, a childhood tumor. When I found that these exogenous opioids altered growth of these developing animals, I decided to see if these exogenous opioids could depress the growth of cancer. Lo and behold, they did so in tissue culture. This started in 1977-1978.

We then progressed to injecting cells into mice and creating cancers, and examined whether these exogenous opioids would repress growth of these cancers. In fact, they did. In order to see if these exogenous opioids exerted their action through an opioid receptor (opioid receptors were discovered in 1972 and endogenous opioids - enkephalins first and then endorphins - in 1975), we had to use an opioid antagonist with the exogenous opioid to see if we could neutralize the effect of the exogenous opioid. We chose to use naloxone, a pure opioid antagonist discovered (with naltrexone) in 1960 by Blumberg and Dayton (they were working for a drug company and searching for compounds that were like heroin/morphine but were not addictive, and these opioid antagonists were some of the chemicals they synthesized; remind me one day to tell you more about Blumberg and Dayton's story on this).

So we injected mice with neuroblastoma cells and then used either the exogenous opioid (in this case heroin), the exogenous opioid and naloxone, or naloxone alone to make sure that the naloxone had no action itself on the cancers. We expected that if the heroin was repressing growth through an opioid receptor, the cancers would grow the same as controls when they were given heroin and naloxone (the naloxone would block the effect of heroin because it preferentially displaces this at the opioid receptor), and that naloxone alone would have no effect. Yes, the heroin made the tumors grow smaller, and yes the heroin/naloxone combination yielded animals with tumors that grew the same as controls - suggesting that heroin worked on tumorigenesis by way of an opioid receptor.

A complete surprise was that the naloxone animals also had delays in expressing the cancers, and in some cases these animals surpassed the effects of heroin. This was shocking to us, yet exciting. I remember going to a major scientific meeting in Anaheim, California in 1979 or so in order to present these exciting (at least I thought so) findings. I went to the assigned room to present my paper and my wife accompanied me. In the meeting room was the projectionist, the speaker before me, and the chairman of the session. When I got up to speak, the person speaking before me left and I presented the 15-minute paper to my wife, the projectionist, and the chairman of the session. So much for the illustrious beginnings of "LDN"!!! The laugh is that 3 years later we received over a million dollars in funding from NIH on our projects, and published 2 papers in Science heralding the discoveries (and this is where naltrexone enters the picture).”

http://ldn.proboards3.com/index.cgi?board=announcements&action=display&thread=884

He has also been heavily involved in the LDN trials on Crohn’s disease and Parkinsons:

http://www.medvision.org/mihpf/medinsight%20-%20ldn%20-%20Press%20Release%20-%20January%2030,%202007.pdf

http://dailystrength.org/c/Parkinsons_Disease/forum/423717-new-parkinsons-study-low

So, it seems to me his words may have been taken out of context for that article, at least by me. I think what he was really saying is that even though LDN isn’t currently a recommended/approved therapy for MS . . . thousands of people are claiming it works. His recent mouse studies endorse the value of the use of LDN for a MS-like animal disease.

Cherie