Article Dr. Natalie Eaton-Fitch Discusses Repurposed Drugs and the Treatment of Myalgic Encephalomyelitis (ME)

1666110217041.png

Dr. Natalie Eaton-Fitch talks with us about low-dose naltrexone (LDN) and the search for a drug to treat myalgic encephalomyelitis. Image courtesy of Dr. Natalie Eaton-Fitch.

1667006362567.png

By Bronc

In the world we live in people are suffering from all kinds of illnesses, which require a variety of different medications to treat them.

Often, the road to finding a novel medication for a particular illness can take many years, as the money for medical trials usually comes from drug companies who have to spend large amounts of money on research and then conduct the different stages of medical trials to ascertain efficacy and safety.

In the myalgic encephalomyelitis (ME) community, we have faced decades of neglect from the medical establishment, who have not put the requisite sums into research. Sadly, it would appear that none of the big drug companies have taken any interest into conducting research into medications to treat ME.

This gap in research has been filled by small groups of researchers at various universities. Rather than wait for years in the hope of some new medication, some scientists have turned to cheap, safe, repurposed drugs as potential treatments for ME.

One such scientist is Dr. Natalie Eaton-Fitch.

Dr. Eaton-Fitch is a research fellow at the National Centre for Neuroimmunology and Emerging Diseases (NCNED) located at Griffith University in Australia. Her research interests include the pathophysiology of ME, Long COVID and natural killer (NK) cells. Dr. Eaton-Fitch’s work is aiming to develop a diagnostic test for ME and to repurpose drugs for the treatment of the illness.

1667006281318.png

Phoenix Rising:

How did you get involved in the field of ME research?

Dr. Eaton-Fitch:

There are a number of reasons — the most significant being that I’ve lived my life watching a family member battle with ME, and have done so for the past 30 years. The other is my interest and enthusiasm in immune biology.​
I reached out to Professor Marshall-Gradisnik at the National Centre for Neuroimmunology and Emerging Diseases (NCNED), Griffith University after I completed my undergraduate degree. I pursued postgraduate studies with Professor Marshall-Gradisnik as my mentor, and I have since been awarded my PhD. I continue working with the team at the NCNED as a research fellow.​

Phoenix Rising:

Naltrexone was originally developed to help people with alcohol and drug addictions. However, in the last 10 years, a small number of doctors have started using low-dose naltrexone (LDN) to treat people with ME. Can you explain how LDN came to be used as a repurposed drug to treat people with ME?

Dr. Eaton-Fitch:

The use of repurposed LDN started in the later 1980s after the positive effects of LDN were reported. LDN has multiple biological functions, including the release of endorphins and immunomodulation.​
Subsequently, LDN was reported to significantly reduce pain, cognitive, and fatigue symptoms in different patient cohorts — for example in multiple sclerosis and fibromyalgia. Indeed, as these are some of the hallmark symptoms of ME, LDN held promise as a pharmacotherapeutic option.​

Phoenix Rising:

A few months ago I listened to a medical lecture by Dr. Keith Berkowitz and Dr. Mobeen Syed, who were talking about the use of LDN to treat patients with Long COVID.
During their presentation, they proposed that the mechanism of action for LDN was to suppress inflammation in the body — which would help to reduce the severity of Long COVID symptoms in many patients.
Can you explain how LDN works to help some people with ME?

Dr. Eaton-Fitch:

Immune system dysfunction is reported in both Long COVID and ME. Naltrexone, while an opioid receptor inhibitor at high doses, acts as an immunomodulator at low doses. LDN increases the release of beta-endorphins, which are a substance involved in many biological functions — including, but not limited to, pain management.​
As an example, endorphins are related to the hypothalamic-pituitary-adrenal (HPA) axis, which is dysfunctional in ME patients and is associated with some metabolic and immune responses.​
Furthermore, immune dysfunction is observed through reduced natural killer (NK) cell cytotoxic activity. (Natural killer cells are innate immune cells that eliminate tumour cells and virus-infected cells. NK cell cytotoxicity refers to their ability to eliminate these target cells).​
NK cells are part of the innate immune system responsible for elimination of viral-infected and malignant cells. LDN is believed to increase NK cell cytotoxic function through the release of beta-endorphins and through restoration of a calcium channel known as transient receptor potential melastatin 3 (TRPM3).​
TRPM3 is a member of a family of transient receptor potential (TRP) ion channels with a vital role in calcium signaling in cells. Calcium is required for a number of biological functions, one of which is immune function.​
Dysfunction of TRPM3 means the passage of calcium into cells is reduced and this impairs cell function and is associated with the symptoms of ME. The restoration of TRPM3 is hypothesised to restore cell function across body systems.​
Here’s another potential mechanism for LDN: (there are quite a few)​
LDN has also been shown to block toll-like receptor 4 (TLR4), a recognition receptor found on immune cells such as microglia. Microglia are immune cells of the central nervous system that are involved in neuroinflammatory responses such as pain, cognitive dysfunction, fatigue, sleep disturbances and mood disorders.​
As neuroinflammation is documented in ME, LDN might regulate TLR4/microglia activity, reducing neuroinflammation, which may relieve the above mentioned symptoms.​

Phoenix Rising:

A small number of medical trials have been conducted into the use of LDN as a potential treatment for ME. Based on the results of these trials how successful has LDN been in helping people with ME?

Dr. Eaton-Fitch:

Current research suggests that LDN is a safe and effective pharmacotherapeutic option for alleviating the symptoms of ME with minimal adverse effects.​

Phoenix Rising:

Some people who take LDN say it has really helped with their fatigue. Others (I include myself in this camp) say LDN has helped with pain issues but not with fatigue issues. How would you explain that?

Dr. Eaton-Fitch:

LDN predominantly has anti-inflammatory and anti-pain mechanisms through the following pathways:​
(i) opioid receptor inhibition;​
(ii) increased endorphin release and activity;​
(iii) TRPM3/immune regulation; and​
(iv) microglia/TLR4 regulation.​
Also, as you’re aware, the presentation and trajectory of ME as an illness varies widely among patients. As this variation may be due to different genetic and functional changes, the response to LDN may also vary. This is why the NCNED also aims to investigate other, but similar, potential pharmacotherapeutic targets.​

Phoenix Rising:

What further research is needed into low-dose naltrexone, in order to prove its efficacy as a treatment for people with ME?

Dr. Eaton-Fitch:

Rigorous placebo-controlled randomised clinical trials are required to further identify the efficacy of LDN in ME.​

Phoenix Rising:

You mention the need for randomised placebo-controlled trials for LDN. On what scale would these trials need to be? Across how many countries? In different subsets of people with ME?

Dr. Eaton-Fitch:

Clinical trials go through a series of phases to test the safety and effectiveness of drug candidates. These phases start with small cohorts before moving into larger cohorts.​
Small-scale trials are currently demonstrating that LDN is safe and effective in improving symptoms of ME. Large-scale clinical trials involving several hundred, then subsequently several thousand participants (meeting more recent diagnostic criteria such as CCC or ICC) will be needed to approve LDN for the treatment of ME.​

Phoenix Rising:

Do you know of any other repurposed medications that are being used by researchers as possible treatments for people with ME?

Dr. Eaton-Fitch:

There are numerous medications used off-label for targeting specific symptoms of ME. However, there is little evidence regarding efficacy.​
The off-label use of Aripiprazole, used to manage symptoms of mood in mental health disorders, has gained interest recently as a potential pharmacotherapeutic option for ME. At low levels, Aripiprazole stimulates dopamine production, affecting cognition, sleep, mood, inflammation, energy production and movement.​

Phoenix Rising:

Can you tell us about your own research into low-dose naltrexone as a potential treatment for ME?

Dr. Eaton-Fitch:

At the NCNED we aim to identify a diagnostic/screening test for ME patients and to discover pharmacotherapeutic treatments to improve symptoms and quality of life.​
We previously reported on impaired TRPM3 ion channel function and associated signaling pathways in ME patients. Thus, TRPM3 ion channels provide a pharmacotherapeutic target.​
TRPM3 ion channels are calcium channels located on various cells throughout the body. When activated, these channels open to allow calcium to flow into the cell, where calcium acts as a secondary messenger to help stimulate cell function — for example to stimulate NK cell cytotoxicity.​
TRPM3 ion channels also respond to various threats/stressors such as infection, allergens, chemicals, surgery, changes to temperature and are involved in inflammatory and pain responses (nociception). Genetic, expression, and functional changes in TRPM3 have been reported in NK cells of ME patients.​
We demonstrated that naltrexone treatment of isolated NK cells from ME patients restored the TRPM3 ion channel function, and subsequently confirmed the efficacy of LDN by demonstrating benefit in the pathophysiology of ME.​
Therefore, our future research aims to complete a clinical trial into the therapeutic efficacy of LDN in ME. Research at the NCNED will focus not only on TRPM3 ion channel pathology, but also on changes to brain MRI in response to LDN.​
1667006309811.png

Bronc is a former historian who is active in his local ME support group. He enjoys interviewing scientists involved in ME research to help himself and others better understand their illness.
 
Last edited by a moderator:
Always nice hearing about the research going on at the NCNED which hopefully will contribute to prescription available treatments in future.

Dr. Fitch and the rest of the team were actually kind enough to lend their time and knowledge to a friends' university documentary project about ME/CFS earlier in the year. Its always a nice reminder to see there are researchers out there trying their best to help the cause in any way :)
 
Hello. I have a question for Dr. Eaton-Fitch. Have you tried LDN on the member of your family? What was the outcome? I'm a long-term sufferer myself (age 75) and would be interested in your personal experience.

Thanks for taking us on....it truly does mean a lot. If anyone has an e-mail address, I would be happy to send this question myself. Yours, Lenora
 
Hello. I have a question for Dr. Eaton-Fitch. Have you tried LDN on the member of your family? What was the outcome? I'm a long-term sufferer myself (age 75) and would be interested in your personal experience.

Thanks for taking us on....it truly does mean a lot. If anyone has an e-mail address, I would be happy to send this question myself. Yours, Lenora
I haveaapssed your question on to Dr.Fitch, fingers crossed she has the time to reply.
 
Ah, Bronc!...Thanks so much for trying to pass this question on. Very kind of you and wouldn't we all be interested in the answer to it? Yours, Lenora
 
Dr.Eaton-Fitch, I hope you will also concider testing LDN injektion for us who have CFS with bad chemical sensitivity preventing us to use oral medication. I have tried LDN as a pill and it helped but I couldn't continue using it because it caused really bad inflammation to my bowel and my mucouse membranes became very sore and swollen, which happends to me with every medicine and supplements too.
 
Ah, Bronc!...Thanks so much for trying to pass this question on. Very kind of you and wouldn't we all be interested in the answer to it? Yours, Lenora
Hello. I have a question for Dr. Eaton-Fitch. Have you tried LDN on the member of your family? What was the outcome? I'm a long-term sufferer myself (age 75) and would be interested in your personal experience.

Thanks for taking us on....it truly does mean a lot. If anyone has an e-mail address, I would be happy to send this question myself. Yours, Lenora
Please find Dr. Fitch's response to your question:

"In response to the question, he [a family member - Bronc] has started LDN on his own accord and has done this separate to our research given the conflict of interest. Starting slow because of history of chemical sensitivities and is yet to reach target dose as he started within the last week. As this is recent, I can’t give an update on personal experiences unfortunately. I would recommend reaching out to support groups for other personal experiences with LDN. Also, visit https://ldnresearchtrust.org/ for FAQ and resources.''

"part of our research outcomes at the NCNED is to transform policy and provide evidence for clinical guideline reforms. I have good feelings about the future!''
 
Dr.Eaton-Fitch, I hope you will also concider testing LDN injektion for us who have CFS with bad chemical sensitivity preventing us to use oral medication. I have tried LDN as a pill and it helped but I couldn't continue using it because it caused really bad inflammation to my bowel and my mucouse membranes became very sore and swollen, which happends to me with every medicine and supplements too.
I have passed your comment onto Dr.Fitch. If she replies I will pass it on.
 
I wonder if the reason some feel better for a day or so when they get a cold (for me the day before) is because the virus stimulates TRPM3 ion channels. 🧐
 
It would be good if they could trial immunovir and cycloferon, that have increased nk cell function in a few members here.
LDN was used by many on PR and the success rates were quite low. I just feel we are barking up the wrong tree looking at LDN. That's my 5cent opinion on it.
 
Thanks to you and Dr. Eaton-Fitch for her response. I have to find a new neurologist (death of one I've had for 35++ years), and this will be difficult.

However, I'd be willing to try, if the one I'm hoping to go to is amenable. If I try, I'll get back to all of you, although I don't expect an appt. until sometime next year.

@heapsreal.....We're all different and what works for one person, won't necessarily work for the next. It gets harder (to say the least) when we have to start over again with someone we've had a relationship for so long. I'm hoping to cut down on my nos. of doctors, but some are just necessary. In my case, a neurologist is definitely one I need. (Several neurological illnesses.) Yours, Lenora
 
We're all different and what works for one person, won't necessarily work for the next. It gets harder (to say the least) when we have to start over again with someone we've had a relationship for so long. I'm hoping to cut down on my nos. of doctors, but some are just necessary. In my case, a neurologist is definitely one I need. (Several neurological illnesses.) Yours, Lenora
I agree with but I think if one looked over all the blogs on LDN, it was a low percentage effect on mecfsers. I'm not saying people shouldn't try it. But for research dollars I think could have been directed at something that's more helpful for a large percentage of mecfsers.

Not sure what you are explaining about your neurologist as I was only talking about LDN.

Cheers
 
I agree with but I think if one looked over all the blogs on LDN, it was a low percentage effect on mecfsers. I'm not saying people shouldn't try it. But for research dollars I think could have been directed at something that's more helpful for a large percentage of mecfsers.

Not sure what you are explaining about your neurologist as I was only talking about LDN.

Cheers
Have you Red Dr. Olli Polo's large retrospective study on LDN, where it helped approximately 70% of his patients? Or the study from australians, where LDN normalized the ion channel functions of T-cell membranes.
 
Have you Red Dr. Olli Polo's large retrospective study on LDN, where it helped approximately 70% of his patients? Or the study from australians, where LDN normalized the ion channel functions of T-cell membranes.
I've read the study from Australia. The other retrospective study you mention helping 70% of patients no, but ask by how much did it improve by and I'd question how long pts stayed on ldn. I'm just going off my personal experience as well as the many posts over 15yrs here on Phoenix Rising. Many started LDN and probably a significant number said they improved but many of them also eventually stopped taking it due to lack of improvement. Initial improvement is hard to workout if placebo or stopped working for other reasons such as some sort of tolerance.

Personally I think it's cheap and safe enough to try but it never lived up to the hype for most people.
 
I've read the study from Australia. The other retrospective study you mention helping 70% of patients no, but ask by how much did it improve by and I'd question how long pts stayed on ldn. I'm just going off my personal experience as well as the many posts over 15yrs here on Phoenix Rising. Many started LDN and probably a significant number said they improved but many of them also eventually stopped taking it due to lack of improvement. Initial improvement is hard to workout if placebo or stopped working for other reasons such as some sort of tolerance.

Personally I think it's cheap and safe enough to try but it never lived up to the hype for most people.
There were 218 randomly selected patients in Olli Polo's study. They were patients who got their CFS diagnose between years 2010 and 2014. The study consisted 1,7 years of follow up and during that time atleast one symptom was relieved from 73,9% of patients. 18,3% did not get any help from LDN. Side effects were rare, isomnia and nausea during the first few days after taking the first pills.
 
Last edited:
I wonder what Dr. Fitch thinks of taking LDN in the morning vs at night. I have tried both but I must say that it usually works better when taken at night. It does cause insomnia but the effect seems to be somewhat more pronounced and longer lasting.
 
There were 218 randomly selected patients in Olli Polo's study. They were patients who got their CFS diagnose between years 2010 and 2014. The study consisted 1,7 years of follow up and during that time atleast one symptom was relieved from 73,9% of patients. 18,3% did not get any help from LDN. Side effects were rare, isomnia and nausea during the first few days after taking the first pills.
I wouldn't call that successful ie 73.9% had one symptom relieved. People should try it so they can tick it off the list or it works for them.

I was suprised to see Polo saying benzos and lyrica no good for cfs . I've found them some of the most helpful meds. Shows how different people react. Also shows we don't really have a good diagnosis or several diagnostic tests to routinely used for mecfs pts.

The nk testing by Australian researchers was to find a diagnostic test, thats 13yrs ago. Honestly don't know why they don't use the nk testing as apart of the testing/biomarker.
 
Dr.Eaton-Fitch, I hope you will also concider testing LDN injektion for us who have CFS with bad chemical sensitivity preventing us to use oral medication. I have tried LDN as a pill and it helped but I couldn't continue using it because it caused really bad inflammation to my bowel and my mucouse membranes became very sore and swollen, which happends to me with every medicine and supplements too.
I contacted Dr.Fitch about your comment. Please find her reply below:

"Thank you for passing this along! This information is very important to us when designing our protocols, we will ensure our protocol removes as much risk as possible and I have passed this information along to the team.

Much appreciated!

Kind Regards,

Natalie Eaton-Fitch, PhD''