Myalgic Encephalomyelitis Channelopathies

The more we know…

This information was a challenge for me to write coherently. I’m hoping that even if it is hard to understand, it brings awareness that there is innovative research happening that may offer real insight into the diagnosis and treatment of ME.

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The ME International Consensus Primer (ICP) states on page 6 that there are channelopathy impairments (as described below) seen in people with myalgic encephalomyelitis. 

I think this aspect of ME doesn't get enough attention.  In recent years, National Centre for Neuroimmunology and Emerging Diseases (NCNED) out of Menzies Health Institute at Griffith University located in Australia has been doing research into transient receptor potential melastatin (TRPM) channelopathies.  In my experience sharing some of their TRPM research findings with my Dr brings to them an awareness that ME is so much more than "fatigue" and "malaise". 

This line of research gives me hope for diagnosis and treatment options that may get at the root of what is causing symptoms in ME.

Our cat Pugsley watching for birds to visit our bird feeder.

What are channelopathies?

This paper on channelopathies states that channelopathies are diseases that develop because of defects in ion channels.  

Scitable by Nature Education explains that ion channels are: 

“…passageways, or ion channels, have the ability to open and close in response to chemical or mechanical signals. When an ion channel is open, ions move into or out of the cell in single-file fashion. Individual ion channels are specific to particular ions, meaning that they usually allow only a single type of ion to pass through them. Both the amino acids that line a channel and the physical width of the channel determine which ions are able to wiggle through from the cell exterior to its interior, and vice versa. The opening of an ion channel is a fleeting event.”

I visualize gates that allow vital nutrients (calcium, magnesium, zinc, etc) to enter our cells.  When those gates are not working, many diseases can arise. 

This paper, Ion Channelopathies of the Immune System states:

“Channelopathies have been widely studied in many organ systems and linked to diseases such as epilepsy, ataxia or migraine in the nervous system, Brugada syndrome, long QT syndrome and atrial fibrillation in the heart, cystic fibrosis, neonatal forms of diabetes mellitus and polycystic kidney disease, to name a few…”

This malfunction of the way nutrients get into our cells may explain why blood work shows we have normal levels of vitamins and minerals in our system, but our symptoms look like we are deficient.

I have experienced more stability in my quality of life from a regular use of supplements, but my symptoms persist.  Considering that channelopathies may be interfering with my ability to absorb nutrients into my mitochondria, I think it is best to have an abundance of nutrients available.  A broken system combined with lack of nutrients would surely compound the issues caused by channelopathies.  

Unfortunately, using supplements may have little impact if the gates to the cells aren't letting anything into the cells.  I wonder if post-exertional neuroimmune exhaustion may be exacerbating the channelopathies which could explain systemic crashing as well as explain different levels of severity.  I would like to see the most seriously ill patients be tested for TRPM channelopathies and compare the results to those who are more moderate.

Channelopathy research in Myalgic Encephalomyelitis

To me it looks like the leading channelopathy research team for Myalgic Encephalomyelitis is NCNED.  I’m not aware of any other ME researchers pursuing this line of research.

Their work shows they understand the importance of stratifying patients including using the International Consensus Criteria (ICC) for patient selection.  That makes sense, because Don Staines and Sonya Marshall-Gradisnik of NCNED were involved in the Canadian Consensus Criteria (CCC - precursor to the ICC) and the ICC, as well as the International Consensus Primer. 

The paper, Altered TRPM7-Dependent Calcium Influx in Natural Killer Cells of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients, published June 26, 2023 states: 

“The outcomes reported here potentially reflect TRPM3 dysfunction identified in this condition suggesting that ME/CFS is a TRP ion channelopathy.”

(ME/CFS used here refers to the Canadian Consensus Criteria.)

What are TRPMs?

This paper, Structural Mechanisms of TRPM7 Activation and Inhibition, gives helpful background on TRPMs including the numbering system used for each TRPM category.  It states: 

“… melastatin-type transient receptor potential (TRPM) ion channels are involved in numerous biological processes, including oxidative stress, cell death, mineral homeostasis, and regulation of vascular tone,...”

This reminds me of the importance of offsetting oxidative stress known to happen in people with ME.  See my previous Substack post HERE that talks about oxidative stress in ME.

The paper, Molecular Mechanism of TRP Channels, states:

“Transient receptor potential (TRP) channels are cellular sensors for a wide spectrum of physical and chemical stimuli. They are involved in the formation of sight, hearing, touch, smell, taste, temperature, and pain sensation. TRP channels also play fundamental roles in cell signaling and allow the host cell to respond to benign or harmful environmental changes.”

I wonder if this would explain the pain and sensory processing issues that are well known in ME.

TRPM research leads to treatment options

The team at NCNED published Naltrexone Restores Impaired Transient Receptor Potential Melastatin 3 Ion Channel Function in Natural Killer Cells From ME/CFS in 2019.

That paper states: 

"The opioid antagonist NTX [naltrexone] has the potential to negate the inhibitory function of opioid receptors on TRPM3 in NK cells from CFS/ME patients, resulting in calcium signals remodelling, which will in turn affect cell functions, supporting the hypothesis that NTX may have potential for use as a treatment for CFS/ME. Our results demonstrate, for the first time, and based on novel patch clamp electrophysiology, potential pharmaco-therapeutic interventions in ME/CFS."

NOTE:  CFS/ME = ME/CFS = Canadian Consensus Criteria in this study.

I have found taking low dose naltrexone (since 2014) has improved my quality of life.  While it has been reported that many find some symptom relief from low dose naltrexone, some with ME have not found it helpful or even tolerable.  More research is needed to understand how naltrexone may be affecting channelopathies.  This handout from ME International gives some information about using low dose naltrexone. 

NCNED also published Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from CFS/ME patients which states: 

“Impaired TRPM3 activity was validated in NK cells isolated from CFS/ME patients using different pharmacological tools and whole-cell patch-clamp technique as the gold standard for ion channel research. This investigation further helps to establish TRPM3 channels as a prognostic marker and/ or a potential therapeutic target for CFS/ME.”

Hope for the Future

This line of research gives me hope that we are finally looking at core causes for symptoms seen in ME.  Many research papers published over the years focused on downstream symptoms that are seen in many diseases. 

Researchers that use the ME-ICC for research and focus on abnormalities specific to ME, give me hope for faster progress going forward.  Of course the key factor is research funds. 

The more that patients and advocates understand about what kind of research is being done, the better we can advocate for funding those researchers who are most likely to find answers for people with ME.

More ME specific research can be found in the list of ME-ICC research discussed in my previous Substack titled Myalgic Encephalomyelitis Research. 

I welcome feedback. Subscribers can reply via email.

Colleen

P.S.: A reader has reminded me that Greg Crowhurst has written about channelopathies. If anyone is interested, this blog post from 2017 is worth checking out. https://carersfight.blogspot.com/2017/02/channelopathy-important-issue-for-those.html

Information provided here or in comments is not to be considered medical advice