This page contains links and information about Intravenous Immunoglobulin
for post-polio syndrome.
IvIg update from Post-Polio Health International
There are a number of other articles at
Post-Polio Health International
Just type IvIg into the search box.
July 2012 - Intravenous immunoglobulin treatment of the post-polio syndrome:
sustained effects on quality of life variables and cytokine expression
after one year follow up. Gonzalez H, Khademi M, Borg K,
Olsson T.
Comments and links for Xepol
January 2007 - Paper by Farbu E, Rekand T, Vik-Mo E,
Lygren H, Gilhus NE, Aarli JA
September 2006 - Paper by
Dalakas.
June 2006 - Paper by Gonzalez H, Stibrant Sunnerhagen
K, Sjoberg I, Kaponides G, Olsson T,
Borg
K.
March 2006 - Paper by Kaponides G,
Gonzalez H, Olsson T, Borg K.
2004 Article from Medline
-
Intravenous immunoglobulin in postpolio syndrome
Some Discussion on Immunoglobulin Therapy for PPS
Subject Xepol, a Treatment for PPS?
From "GG Genereau"
A very interesting article!
GG
http://www.pharmalive.com/News/index.cfm?articleid=566113&categoryid=40
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Subject Re Xepol
From James
Hi
The article about the positive effects of Xepol was very interesting.
My wife has had two treatments with Xepol with Dr Henrik Gonzalez, both
successful.
Let me give you some background. She had polio in her lower body in 1944 as a toddler, and was left with a thinner, shorter and weaker right leg, and a slight limp. She led a normal day-to-day life, with few limitations.
Everything was fine until the mid-nineties, when she started suffering from tiredness and e g felt unable to carry groceries or do physical work. Even walking a few hundred yards made her tired. She was diagnosed with PPS in 1999.
Xepol was offered to PPSers in 2002, and she was one of the Phase one patients who received Xepol. The treatment involved three days at a clinic, four-five hours per day, with intravenous feeding in an arm or hand, resting during the treatment. Afterwards she felt she had more energy, was less tired, and had a feeling of general well-being. Her leg muscles felt stronger.
She received her second Xepol treatment in June 2005. The treatment was similar to 2002, and the results were the same.
What about other patients? One woman suffered from migraines during the treatment and had to stop, another felt her health deteriorated afterwards; others felt their general condition had improved.
She was suggested not to take part in the third treatment last year, as they wanted to have more new patients.
Nowadays she uses two canes for walking outside, as otherwise she risks aching knees and hips; with the canes this never happens. She still needs a lot of sleep; 10-12 hours every night, and an occasional afternoon rest.
Her overall feeling is that Xepol has helped her, and slowed down the ongoing effects of PPS.
She will probably take part in future treatment if it is offered.
Regards
James
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Subject Re Xepol
From "Patrick"
I found this. http://www.malargarden.se/eng/rehab_xepol.html
Pat
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Subject Re Xepol
From Bill
Yes, I did some reading after my first post and realized that is was an immunoglobulin treatment.
I actually asked Dr Silver about this a couple of years ago and she was aware of the research but hesitant to endorse it at the time. And, treatment would be very expensive ($10,000 or so).
I did find Dr Silver's most recent thoughts on immunoglobulin...
http://www.post-polio.org/edu/pphnews/pph22-3p4-5.pdf
Subject: Some Discussion on Immunoglobulin Therapy for PPS
From: Ron
I read the article from Post-Polio Health about Immunoglobulin
treatment for PPS with interest. They report an 8.6% improvement on
average in muscle strength with people with PPS. I find this to be an
impressive statistic. They also report that a course of Immunoglobulin
treatment would be an infusion once a day for 3-5 days at the cost of
about $10,000 a course. My question, assuming that this research is
successfully replicated, is how long does a course of this treatment
last? How often will it be required to, at the least, arrest the
continual deterioration of muscle mass?
Ron
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From: "Brenda"
Ron,
More detailed information about the study is at www.post-polio.org
,
in the spring 2006 edition, vol. 22, no. 2. The information you read
is in the summer 2006, vol. 22, no. 3 article. A variation of this
article was also in the Polio Outreach of Washington spring 2006. In
this article it states "We next developed a multi-center
placebo-controlled study, double-blinded in 135 post-polio patients.
(In the former study we used 90 grams of IvIg; 30 grams daily for 3
days.) In this study we used 30 grams for 3 days, repeated twice. We
noted an increase in muscle strength of 4.3% in the post-polio
patients. In the placebo group, muscle strength was decreased by
5.7%. The natural course of decrease in strength was 5.7% in one-half
year."
Based on the above "30 grams a day for 3 days, repeated twice," this
is a total of 9 days of 30 grams of immunoglobulin. The timeframe of
the study is one-half year, the above 4.3% increase in muscle
strength is over a one-half year timeframe. I would assume that the
treatment would need to be repeated every 6 months.
It would be nice to find a clinical trial in America using
immunoglobulin treatment for post-polio.
Brenda
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Subject: From Dr. Borg about IVIG
From: Post-Polio Health International
PHI received this response about IVIG from Dr. Borg, Professor and
Chair, Karolinska Institutet, Div of Rehabilitation Medicine, Danderyd
Hospital, Stockholm.
We have preliminary results from follow-up studies showing that the
cytokine levels in the cerebrospinal fluid is significantly decreased
one year after the treatment. There is a statistical improvement of
quality of life 2 years after the treatment. For the individual, the
effect may last from 6 weeks to several years.
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Subject: Re: From Dr. Borg about IVIG
From: EDWARD BOLLENBACH
<snip>
The second thing, which I think may have profound importance to those of
us with PPS is that proinflammatory cytokines, like Tumor Necrosis
Factor alpha, and several interferons also present, damage tissue. If
Spinal tissue is damaged over 20 or so years and then if the culprit
cytokines are removed with IVig how long will it take to realize
improvement? Will there be resprouting over a long time? Are there
enough living myofibrils (muslce fibers or cells) to make a big
difference? All of these questions remain unanswered.
The other thing, which has tangential relation to Borg, is that Insulin
like Growth Factor-1 was tried early on to see if it would stimulate
resprouting as it does in the normal spine. In PPS subjects these
experiments were dissappointing. As little as billionths of a gram of
Tumor Necrosis Factor in the cord will change the conformation of the
IGF receptors on motor neurons so that no Insulin like Growth Factor
will be taken up. Those who have undergone Borg/ Gonzalez treatment need
to then try IGF but I haven't seen anything of this anywhere. Researchers???
Eddie
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From: Rick
The Borg paper stated that the research finding had a p valuse of
0.029. While I agree with the statement "any p value less than 0.05 is
significant", note that most studies that return really meaningful
results have p values of 0.01 or less and most usually less. The p
value from Borg's data is almost 0.03. I only mention this to note that
the increase in muscle strength following the use of IV immunoglobulin
statistically is not that great.
Consider this in light of the possibility of side effects from this
therapy including the possibility of HIV if the source of the
immunoglobulin is human and not recombinant. And keep in mind that the
median increase in muscle strength is only 8.3%. Seems like a lot of
downside risk for a minimal potential upside benefit.
Just my thoughts on this.
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Subject: Re: From Dr. Borg about IVIG
From: EDWARD BOLLENBACH
Rick (MDK) wrote:
The Borg paper stated that the research finding had a p valuse of 0.029. While I agree with the statement "any p value less than 0.05 is significant", note that most studies that return really meaningful results have p values of 0.01 or less and most usually less.
I agree with Rick above, somewhat. There are side effects and potential hazards to most medical treatments. However, since the inception of use of IVIg there has NEVER been a transmission of HIV recorded. Prion (Mad Cow et alia) is stated as highly unlikely by the British Columbia blood study group. For their booklet on IVIg safety see
http://www.pbco.ca/documents/ivighandbook1.pdf#search=%22IVIg%20and%20prions%22
They test for HIV, and several other viruses and donors are also screened for these before donation. . I'd like to try to clarify what a p value is in statistics.
When you do a statistical test you set your confidence levels and .05 is just fine as is .01. .01 isn't "really" meaningful while .05 "isn't really" meaningful. Depending on the study characteristics I would have set at .05 too because CNS damage in PPS isn't likely to resolve immediately on administration of IVIg. What p=.05 means is that anything below that, like .029 is the probability that the resulting 8.3% improvement would occur by chance alone and the IVIg really had nothing to do with the result (a gain in strength measured at 8.3%.) So, if the IVIg treatment showed an average 8.3% improvement (which could mean for someone with PPS the difference between being able to do something and not being able to do it) a p value of .03 indicates a 97% chance the IVIg was responsible for the improvement. This is a significant result because the researchers determinined anything under .05, 5% p is the acceptable line for significance. The researchers would have called the result insignificant if they got a .06 p value because there would be a 6 percent chance the results were simply chance. That's not too high either. With a p value of .01 set before the experiment the researchers are saying the result will not be accepted as significant unless there is less than a 1% chance that the result was due to chance and not whatever they did to the experimental group of people or animals or whatever. Dr. Marcia Falconer, my friend an co-writer, agrees with the fear of transmission of prion diseases like mad cow etc., Many of these diseases have a 20 or more year incubation period and are rare. As a microbiologist I have not kept up with prion biology and don't know how much material may be needed or even if it is in the blood. These diseases are generally brain diseases that have to do with brain protein alterations tripped off by an altered protein. However, although I am unfamiliar with the manufacture and concentration process for IVIg British Columbia Province Blood researchers say such transmission is highly unlikely.
The one thing you should keep in mind about IVIg is that there is also a very small risk of kidney failure. I think there have been some 200 cases of this reported as a result of the tens or hundreds of thousands of IVIg infusions. It is not likely at all. The NIH regards the procedure as safe and effective for the treatment of many diseases. I include below a statement about the use of IVig for various illnesses in a statement from the National Institutes of Health about it's safety You should also know that about 20% of it's use is for off label uses by neurologists, mainly.................Cheers...........Eddie
From http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat4.section.7663
In response to the question, "What are the risks involved in the use of IVIG?" the consensus panel concludes that they are minimal. However, appropriate means to monitor IVIG for contamination with potential pathogens should be developed. In response to the question, "What are the mechanisms of action of IVIG?" the panel concludes that in most circumstances present hypotheses are speculative and not proven. In response to the question, "What are the directions of future research?" the panel concludes information concerning mechanism of action is critically needed. Deriving information concerning mechanisms of action or other potential uses of IVIG from clinical experiments and trials is costly and inefficient. Without knowledge concerning anticipated objective physiologic end points, trials to establish effective therapeutic regimens are empiric and new initiatives largely exercises in serendipity.
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From: Rick
http://en.wikipedia.org/wiki/P-value
Hi Kath,
Above is a link to Wikipedia that gives a good explanation of the whole concept of p-value; this will explain this concept better than I can. I am not a statistician, but I am a scientist and I encounter these terms routinely in published medical literature. I do know that I would consider side effects or pharmacologic effects with p-values in the range that we are discussing as not being that significant because of a decreased possibility of being reproduced. Then when you consider the realm of side effects from this therapy, its not like there is not risk.
Just my thoughts.
Rick
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Subject: IVIg substitute for PPS?
From: Eddie Bollenbach
Newswise - By pinpointing the mechanism through which an intravenous therapy combats chronic inflammatory diseases, researchers have discovered that they may be able to replace the time-consuming infusion therapy with an injection that could be given during a quick office visit. Investigators at Hospital for Special Surgery in New York City have discovered that intravenous immune globulin (IVIG) or antibody therapy works, in part, by attaching to a receptor known as Fc?RIII and blocking the function of interferon gamma, a major inflammatory factor. Only a small component of the IVIG solution, 0.5%, is responsible for blocking this receptor.
"The study suggests that it's not the whole preparation itself, but the immune complexes within the preparation that are causing the therapeutic effect," said Lionel Ivashkiv, M,D,, director of Basic Research at Hospital for Special Surgery (HSS) who led the study. Instead of using IVIG, which is pooled from thousands of blood donors, clinicians may be able to use small amounts of so-called immune complexes, or even design synthetic drugs that will avoid problems, such as potential exposure to infectious agents, that are associated with using blood products.
The study appears in the January issue of the journal /Immunity/ .
For years, doctors have used IVIG to treat patients with autoimmune and chronic inflammatory diseases, such as dermatomyositis, Kawasaki disease, multiple sclerosis, lupus, chronic lymphocytic leukemia, and idiopathic thrombocytopenic purpura, but just how the therapy works has remained a mystery. Some researchers have shown that IVIG works, in part, by activating a receptor known as Fc?RIIb, which then suppresses auto-antibody-mediated inflammation. HSS researchers wondered whether an immune system protein called interferon gamma (IFN-?) could be involved-many chronic inflammatory and autoimmune diseases are caused or exacerbated by an overexpression of this protein.
To test their theory, the investigators turned to macrophages, immune cells that engulf bacteria and are stimulated to kill their prey by IFN-?. The researchers found that in test tube studies of macrophages, IVIG could inhibit the action of IFN-? signaling.
Next, they tested the effects of IVIG in mice infected with Listeria monocytogenes, a bacteria that is usually controlled by IFN-?. They found that mice treated with IVIG, because of the suppression of IFN-?, had much more severe infections than mice treated with saline. Experiments in a mouse model of immune thrombocytopenic purpura also revealed that immune globulin inhibited IFN-?. IVIG sparks this inhibition by docking on a receptor called Fc?RIII.
In another experiment, researchers turned their focus to a different question-which component of IVIG is responsible for its therapeutic effects. IVIG is composed of 99.5% monomeric IgG and 0.5% so-called immune complexes. The researchers cultured macrophages with the different IVIG components and discovered that the immune complexes were responsible for the suppression of IFN-?.
"This study suggests that we can move away from using these IVIG preparations and generate very defined (synthetic) immune complexes, which have the potential to work better, be easier to deliver, and have fewer problems in terms of the infusion part of the therapy," Dr. Ivashkiv said.
Usually, patients must receive IVIG infusions in the hospital setting, which can involve three to four hours per day, for three consecutive days. "IVIG is time intensive, it's somewhat expensive, and there are sometimes shortages, because it's a human product," Dr. Ivashkiv explained. "A lot of the limitations of the therapy is just the volume and the quantity of the material that is used. Some people get volume overload or severe allergic reactions."
If clinicians can deliver only the active agent of IVIG and/or design immune complexes with recombinant materials, they may be able to avoid many of these problems, say researchers. "It could be done as an injection, as part of an office visit," commented Dr. Ivashkiv.
In addition to HSS researchers, investigators from the Weill Medical College of Cornell University and Weill Graduate School of Medicine, Memorial Sloan-Kettering Cancer Center, Beth Israel Deaconess Medical Center, the British Columbia Cancer Agency in Vancouver, and the Walter and Eliza Hall Institute of Medical Research in Australia contributed to the study. A Cancer Research Institute Fellowship and the National Institutes of Health supported the work.
About HSS Founded in 1863, Hospital for Special Surgery is a world leader in orthopedics, rheumatology and rehabilitation. A member of the NewYork-Presbyterian Healthcare System and an affiliate of Weill Medical College of Cornell University, HSS provides orthopedic and rheumatologic patient care at NewYork-Presbyterian Hospital at New York Weill Cornell Medical Center. All HSS medical staff are on the faculty of Weill Medical College of Cornell University. Its Research Division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. The hospital is located in New York City. For more information, visit http://www.hss.edu .
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