A Chronic Fatigue Syndrome/POTS Patient Responds to a Multiple Sclerosis Drug - What Does It Mean?

[Ken Shield]

@Ken Shield I didn't, unfortunately. I noticed a dramatic improvement in my fatigue. But almost as soon as I was able to tie this improvement directly to Copaxone, I had the allergic reaction. It was so dramatic and I was so desperate to continue taking it that I even went to an allergist to confirm my allergy. It might have been a one time thing. But he did the standard skin tests and found me to be quite allergic. I have developed many allergies in recent years since I've been sick. I'm now allergic to penicillin and ginger - plus its relatives like turmeric.

Only 3 years in, but the best I've felt was while using prednisone for a couple different chest colds and skin rash issues. I know it's not recommended for long term but wow did I feel great. Yet, the numbness and tingling in my feet still continued.

 

[Veet]

Mine is low dose Naltrexone (LDN), my insurance is not covering it compounded. Trying to get a Dr to prescribe in 50mg tablets and I can do the math and make it into 1mg/ml solution. Might resort to buying it online!

GG

Online is easy and reliable. I use alldaychemist.com. You can leave the rx section blank.

LDN clearly increased my stamina. I reckon that has to do w/ lowering inflammatory processes.

It’s hard to summarise such a complex story – you make it look easy,

yes!

I recall that in several of the MRI's I had, the comments on the reports were "small, unexplained lesions in brain".

I also had this in the 1 MRI I had when at my worst. Lucinda Bateman mentions these as possible markers, although mine were dismissed in the radiologist's report.

 

[Merida]

An important discussion. I had a great improvement on 2 weeks of Levaquin - for diverticulitis - believe it or not. Thought I was cured. But symptoms gradually returned. Much later found out that this drug also has immune modulating properties. I appreciate that my immune system has always been 'kinky' - back to childhood - allergies, hives, etc.

 

[GG]

Contrave is the name of the drug I mentioned: it is a compound of 80mg wellbutrin the antidepressant and 8 mg naltrexone. Naltrexone is usually used at doses 50+ for addiction. Contrave is a weight loss drug, if you are under weight or anorexic/afflicted with an eating disorder it would not be advisable to even consider.

My theory was you just cut one of the 80w/8n in half and you basically have a very very mild dose of wellbutrin and about 4mg ldn.

Anyway I mentioned it simply as something to look into if you have no other way to get doctor observed naltrexone. I'm curious @Who Me? What indicates this drug would be unsafe for everyone?

Just sent an email to my Dr and his assistant, see how they respond! So you are not taking this medication?

I was on Cymbalta, but came off it, probably had something to with the weight I have put on, and it was no longer effective for my pain. I have Fibromyalgia as well.

GG

 

[Cort]

I wasn't clear, yeah, they diagnosed me with SFPN. did a tilt table test, which I passed at the time, but think I might not now. Having issues with my blood pressure, running high. No, nothing else going on that I know of.

I was looking to travel to DC area to be part of Dr Barniuk's study with the exercise, but I am stuck in a limbo while applying for disability now. Going to have to go see Drs for that, and not sure I have a solid ride for back and forth. Hope they recruited all the ME/CFIDS/CFSers they needed!

GG

Edit: Part of the reason I wanted to do the Barniuk study is I did the CPET test in 2010, so would be interested to see if things have changed in that area.

You are the man GG for getting in all these studies in particular the CPET one....I hope you can get in the next one...

Was Oaklander looking for ME/CFS patients or FM patients or did she differentiate?

 

[Cort]

Many people, especially as they get older do get white areas on their brain that can look like MS lesions. Look it up on the 'net. People who develop Alzheimer's have whitish plaque on their brain. That does not mean everyone with white spots (seen through a brain scan-CT) will develop MS or ME or Alzheimer's Disease.
I've had a brain scan and their are white areas seen but not quite consistent with MS. I do have POTS, leaky gut syndrome, IBS, FM and ME. Now I suppose you could say I have multiple diagnosis but not if you understand ME/CFS (read the Canadian Consensus) there are many, many symptoms when taken individually can be labelled as individual diseases or syndromes. Put them together and you have what is, at least now, called ME/CFS.
Maybe I'm missing what some of the other members were trying to say???

The good news of this article is that there may be hope for a disease, that nobody seems to be able to figure out, that is somewhat similar to MS, Polio etc and the drugs used for these conditions may in fact help ME/CFS. Yes, there may be millions of people dx with MS when indeed they have ME or vs vs. And yes, sometimes the drugs that help these conditions are very powerful and can cause severe side effects, damaged liver etc. Think about cancer drugs. One would have to make a choice when offered such a drug, weigh the options. The lessor of two evils.

Twenty years ago I had lesions that were not consistent with MS either. I was having neurological symptoms and put on a watch list but the symptoms thankfully mostly disappeared.

 

[Ms Nancy Blake]

You are the man GG for getting in all these studies in particular the CPET one....I hope you can get in the next one...

Was Oaklander looking for ME/CFS patients or FM patients or did she differentiate?

I'd be interested to know how long after the two- day test before you returned to your pre-test level of functioning?

 

[Cort]

Look what I just found - Copaxone is also a microglial inhibitor

Glatiramer acetate (aka Copaxone) is an immunomodulatory drug which has been shown to reduce microglial cell activation in M.S., modulates TNF-1 and IL-10 expression in microglial cells, and is believed to have other neuroprotective properties.

http://www.cortjohnson.org/blog/201...-fibromyalgia-chronic-fatigue-syndrome-mecfs/

 

[Annesse]

I think the reason for the dramatic improvement on Copaxone (glatiramer acetate) may be due to the fact that it inhibits immune cells called dendritic cells (see following study).


Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo.
Weber MS, Starck M, Wagenpfeil S, Meinl E, Hohlfeld R, Farina C. 2004. Brain 127(Pt 6):1370-8. Epub 2004 Apr 16.

“It is widely assumed that glatiramer acetate (GA), an approved agent for the immunomodulatory treatment of multiple sclerosis, acts primarily as an antigen for T lymphocytes. Recent studies, however, indicated that in vitro, GA directly inhibits dendritic cells, a rare but potent type of professional antigen-presenting cell (APC). To investigate whether these in vitro observations are relevant to the actions of GA in vivo, we studied the effects of GA on monocytes, the major type of circulating APC…These results demonstrate for the first time that GA inhibits monocyte reactivity in vitro and in vivo, significantly extending the current concept of the mechanism of action of GA.”



Research confirms the involvement of dendritic cells in both MS and ME/CFS. Dendritic cells release large amounts of inflammatory cytokines such as tumor necrosis factor, interleukin-6, and interferon-gamma. These cytokines are responsible for many of the symptoms that occur in MS and ME/CFS. For instance, elevated tumor necrosis factor is directly linked to reduced cerebral blood flow. Reduced cerebral blood flow can lead to a variety of cognitive deficits (brain fog etc.).

ME/CFS AND BROAD DECREASES IN CEREBRAL BLOOD FLOW

In the following study the researchers found that patients with CFS had "broad decreases" in cerebral blood flow.

Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling.
Biswal B1, et. al. J Neurol Sci. 2011 Feb 15;301(1-2):9-11.

"...The patients as a group had significantly lower global CBF than the controls. The reduction in CBF occurred across nearly every region assessed. The data extend our earlier observation that CFS patients as a group have broad decreases in CBF compared to healthy controls."
http://www.ncbi.nlm.nih.gov/pubmed/21167506

TNF AND REDUCED CEREBRAL BLOOD FLOW

Elevated TNF is directly linked to reduced cerebral blood flow. For example, in the following study the researchers found that TNF caused a "significant, acute" reduction in cerebral blood volume. Notice the study states that TNF is elevated in MS.

TNF-alpha reduces cerebral blood volume and disrupts tissue homeostasis via an endothelin- and TNFR2-dependent pathway.
Sibson NR1, et. al. Brain. 2002 Nov;125(Pt 11):2446-59.

"TNF-alpha expression is elevated in a variety of neuropathologies, including multiple sclerosis...Here, using MRI, we demonstrate that a focal intrastriatal injection of TNF-alpha causes a significant, acute reduction (15-30%) in cerebral blood volume..."
http://www.ncbi.nlm.nih.gov/pubmed/12390971


TNF AND ME/CFS

In the following study the researchers concluded that TNF was "significantly increased" in patients with CFS.
TNF-alpha and chronic fatigue syndrome.
Moss RB1, et. al. J Clin Immunol. 1999 Sep;19(5):314-6.

"Based upon the clinical presentation of chronic fatigue syndrome (CFS), we hypothesized that proinflammatory cytokines may play a role in the pathogenesis of the disease. We therefore undertook a retrospective cross-sectional study to examine the role of TNF-alpha in patients with CFS. Our results suggest a significant increase serum TNF-alpha in patients with CFS (P<0.0001) compared to non-CFS controls..."
http://www.ncbi.nlm.nih.gov/pubmed/10535608


Also, someone mentioned that they felt better on prednisone. Prednisone also inhibits dendritic cells.

 

[Annesse]

Look what I just found - Copaxone is also a microglial inhibitor

Glatiramer acetate (aka Copaxone) is an immunomodulatory drug which has been shown to reduce microglial cell activation in M.S., modulates TNF-1 and IL-10 expression in microglial cells, and is believed to have other neuroprotective properties.

http://www.cortjohnson.org/blog/201...-fibromyalgia-chronic-fatigue-syndrome-mecfs/

Hi Cort - I think we are on the same page. As the following study states, tumor necrosis factor activates microglia. So, I think the sequence is dendritic cells>tumor necrosis factor>activated microglia. Copaxone inhibits the dendritic cells from releasing tumor necrosis factor.


Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial phagocytosis,
Urte Neniskyte,a,b Anna Vilalta,a and Guy C. Browna,

Tumour necrosis factor-α (TNF-α) is a pro-inflammatory cytokine, central to the regulation of inflammation in body and brain. In the healthy brain, it is expressed at very low levels by a variety of brain cells including neurons [29], but microglia (brain macrophages) and astrocytes, activated by pathogens or damage via pattern recognition receptors such as Toll-like receptors (TLRs), express and release high levels of TNF-α [18,13,33,21]. Thus the damaged or diseased brain contains high levels of TNF-α, including during brain trauma, ischemia, and neurodegenerative conditions [8,22]. TNF-α activates microglia and astrocytes via TNF receptors 1 (TNFR1) and 2 (TNFR2) [11], which activate the phagocyte NADPH oxidase (PHOX) [20], caspase-8 [2] and NF-κB [5], resulting in the expression of further pro-inflammatory and phagocytic genes that increase the ability of glia to deal with pathogens and damage [31]. However, high and sustained levels of TNF-α can lead to neuronal damage [10], and there is evidence that TNF-α contributes to a variety of brain pathologies, such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis [8,22]. The mechanisms by which TNF-α is damaging to neurons is unclear, but the inflammatory activation of glia may contribute.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158418/

 

[klassesen]

Cort, how it operates may not be as much as a mystery due to a recent study. This drug causes a significant alteration of gut bacteria. see http:new post //www.ncbi.nlm.nih.gov/pubmed/25775034
or my post at
https://cfsremission.wordpress.com/2016/04/01/copaxone-or-glatiramer-acetate-impacts-on-the-gut/

MS has a distinct major shift of gut bacteria which is being looked at more and more for theraphy.

 

[Deborah Lane]

Some answers may be found in this lecture by Dr. Anne Louise Oaklander of Harvard and Mass General Hospital. Her work on Small Fiber Polyneuropathy shows how extensive the effects are from this type of nerve damage, which until recently was not studied, even though non-myelinated nerves are nearly everywhere and may make up over 80% of an axon which includes a myelinated fiber. POTS, autonomic dysfunction of every kind, aching, fatigue, cognitive issues, weakness light sensitivity, GI symptoms and most of the other symptoms of ME can be caused by this type of neuropathy.

Cort, it would be wonderful if you contacted her for an interview and shared some of our information too. She seems to be a pioneer, making discoveries which could be very useful to us.

Dr. Oaklander happens to be my doctor - she has been the only doctor who actually took the time to listen to me when I first came to her several years ago after spending years being told that my symptoms were all in my head. She is indeed a pioneer.

Most recently she had me tested for a gene mutation which has come back positive for an issue with my sodium channels. I am seeing her next month to begin a new medication that may help my severe pain. I have been dx'ed with Fibromyalgia, SFPN, CRPS, severe endometriosis (had to have a complete hysterectomy at 24yrs), degenerative disk disease, peroneal nerve damage and sciatic nerve damage in my left leg and a good case of depression and PTSD to boot.

Dr. Oaklander helped me come back from being very suicidal simply by taking me seriously and finding the root cause of my pain. Being believed allowed me to keep on going in life, despite the pain. I thank her for this every time I have the privilege of seeing her.

 

[KME]

@KME What a great explanation. Thanks SO, SO much for taking the time to reply!! It made a lot of sense. When I think back to my early years with ME/CFS I recall that in several of the MRI's I had, the comments on the reports were "small, unexplained lesions in brain". There was no other follow up or comments by the doctors other than to say I didn't have MS. I saw 6 different Neurologists during that period, each one more dismissive than the previous one......It was maddening. The only other time I had 'antibodies' was when I was fighting Candida for about 2 years. In the beginning I tested positive for "Candida antibodies" and then later after going through a strict protocol it was at zero. And someone mentioned protozoas in this thread. I took 15 drops of Oil of Oregano (I put them in empty capsules) 3 x day for 6 weeks and was completely rid of a protozoa called Blastocytis Hominus. And, yes my ME/CFS was triggered by a virus, coupled with a near catastrophic reaction to Synthroid (because my adrenals were failing) and severe POTS. So, in that regard I'm a pretty typical patient.

Exactly. You're typical for ME/CFS and ME/CFS specialists (the real ones!) will recognise that. The other doctors are just acknowledging that you're not typical MS/ALS/Parkinson's/rheumatoid arthritis/whatever their diseases are, and hence that they have nothing to offer you, but they sometimes choose to take that extra step and say there's nothing wrong. It would be better if they were happy to say "You have tested negative for the diseases I could help you with." I really appreciate the ones who do that.

 

[KME]

Boy is that an interesting time-line......

Just to thicken the plot a bit more - Tetracycline antibiotics are also microglia inhibitors

• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC28119/

Yes, the timeline blew my tiny mind when I finally put two and two together. Also highlighted how useful it is to keep a diary and how easily we could attribute benefits to the wrong drug/supplement!
Great re microglia inhibition. They seem to have a nice broad anti-inflammatory effect.

 

[Veet]

@Deborah Lane Congrats on the good fortune of having Oaklander for your Doc. I appreciated the vid and her work.

 

[Cort]

Wow...I'm not surprised you had a really good case of depression going there with all that going on.

Thanks for the great recommendation of Dr. Oaklander - a pioneering researcher and a good doctor to boot - the complete package.

Love to hear about that sodium channel mutation and how that goes. Good luck with the new med.

Dr. Oaklander happens to be my doctor - she has been the only doctor who actually took the time to listen to me when I first came to her several years ago after spending years being told that my symptoms were all in my head. She is indeed a pioneer.

Most recently she had me tested for a gene mutation which has come back positive for an issue with my sodium channels. I am seeing her next month to begin a new medication that may help my severe pain. I have been dx'ed with Fibromyalgia, SFPN, CRPS, severe endometriosis (had to have a complete hysterectomy at 24yrs), degenerative disk disease, peroneal nerve damage and sciatic nerve damage in my left leg and a good case of depression and PTSD to boot.

Dr. Oaklander helped me come back from being very suicidal simply by taking me seriously and finding the root cause of my pain. Being believed allowed me to keep on going in life, despite the pain. I thank her for this every time I have the privilege of seeing her.

 

[Cort]

Fascinating stuff Ken! Thanks for pointing that out. Didn't a study show problems with Clostridia in ME/CFS....My Kombucha is definitely helping by the way.

Cort, how it operates may not be as much as a mystery due to a recent study. This drug causes a significant alteration of gut bacteria. see http:new post //www.ncbi.nlm.nih.gov/pubmed/25775034
or my post at
https://cfsremission.wordpress.com/2016/04/01/copaxone-or-glatiramer-acetate-impacts-on-the-gut/

MS has a distinct major shift of gut bacteria which is being looked at more and more for theraphy.

 

[tatt]

@Rachel Riggs I'm not up to commenting on why a particular drug makes you better but I do know a bit about allergic reactions. Have you considered taking the drug but in very tiny amounts to try and build up tolerance and/or also taking antihistamines to reduce the reaction/ eating a low histamine diet/ taking DAOSIN.

 

[Rachel Riggs]

@tatt Yes! That is best accomplished in a medial setting to avoid anaphylaxis - it's called desensitization therapy and I had planned to go that route.

I was just holding off for a scheduled appointment at Stanford with Montoya's PA. I didn't want the Copaxone to affect my lab work in any way.

I explained my plan to the PA at Stanford (Katie) and she said it wasn't an option if I wanted them to treat me. So I chose instead, to give their protocol a shot! I have started on LDN, and will be adding Valtrex in 6 weeks.

 

[tatt]

@Rachel Riggs Fair enough. However you'd only mentioned welts and there is a very big difference between welts and anaphylaxis. One can progress to the other but there are very many more people who experience skin reactions than ever have an anaphylactic reaction. I'm not underestimating how awful skin reactions can be - suffered for 6 months + myself - but the risk of anaphylaxis during desensitisation is different for those who have only had skin reactions and those who have already experienced anaphylaxis.