Solve M.E.’s Chief Scientific Officer, Sadie Whittaker, was on a mission. She wanted to get chronic fatigue syndrome (ME/CFS) embedded in one of the top medical schools in the country.
UCLA, located in the tony Westwood neighborhood of Los Angeles, has an immense and impressive campus. US News and World Reports has ranked its medical school 7th in the country.
Whittaker met with some senior administrators who suggested that she talk to the Iris Cantor Women’s Health Center – a Center of Excellence for Women focusing on both research and clinical care.
The Iris Cantor Center didn’t know much about ME/CFS, but when they learned about the high female predominance, the little funding, and the high prevalence, they were enrolled and invited the Solve ME/CFS Initiative to apply for the Center’s Annual Health Pilot Program.
In this program, the Center solicits proposals for UCLA researchers to study a select number of diseases that disproportionately affect women. Five or six studies are typically awarded each year.
Solve M.E. put together a toolkit about ME/CFS and applied to be one of the featured diseases in the program. Their application was accepted – the Center notified UCLA researchers that it was looking for proposals to study ME/CFS – and the proposals rolled in.
Solve M.E. picked the winner. It turned out to be a rarity for this disease – a small clinical trial no less – to assess the effects of repetitive transcranial magnetic stimulation (rTMS) in ME/CFS. Karl Zeile, a Solve M.E. board member, and Dian Zeile stepped up to support it.
I talked with Dr. Juliana Corlier PhD and Dr. Andrew Leuchter MD about their upcoming study. The director of the UCLA Transcranial Magnetic Stimulation (TMS) Clinical and Research Service, Dr. Leuchter has published over 150 scientific papers, including almost 2 dozen studies on rTMS.
For her part, Dr. Juliana Corlier has a PhD in cognitive neuroscience and is currently an Assistant Project Scientist at the UCLA Neuromodulation Division. She has a special interest in treating pain and fatigue with TMS, and leapt at the chance to see if it could be used to reduce the pain and fatigue in ME/CFS.
I asked Dr. Leuchter how he got interested in magnetic stimulation. Leuchter explained that he was a practicing psychiatrist who was not satisfied with the “serious limitations” of the drugs he was using when he came across magnetic stimulation over a decade ago. The idea of being able to safely rewire the brain to help people feel better intrigued him, and over time he came to specialize in rTMS.
The procedure is remarkably easy on the patients: the participants are awake during the procedure and are able to drive themselves home afterwards. He believes the next generation of small, portable TMS devices that will be able to be used at home will be game-changers for many.
He explained that rTMS has been used for mood disorders for quite some time, but the use of rTMS for pain came about after investigators recognized that it was helping to improve mood problems and reduce pain in some of their subjects.
- Solve ME’s Chief Scientific Officer Sadie Whittaker was on a mission to get UCLA researchers to study ME/CFS.
- After being directed to the Iris Cantor Center for Women’s Health she enrolled them in having ME/CFS be one of the select diseases featured in the Center’s Annual Health Pilot Program. The Cantor Center used the program to ask UCLA researchers to apply to study ME/CFS.
- The winning application – supported by the Weiss family – is using a novel repetitive transcranial brain stimulation (rTMS) technique to damp down the activity of the limbic system and boost up the activity of the prefrontal cortex.
- This could reduce the activation of the fight/flight or sympathetic nervous system, rebalance the autonomic nervous system, reduce fear based messages emanating from the limbic system while boosting cognition, working memory, planning, etc.
- One small rTMS study was successful in ME/CFS. rTMS has been assessed more in fibromyalgia (FM) where it has mostly been successful. A recent FM study found significant pain reductions that lasted at least six months.
- This is the first time in either disease, I believe, that this duo-brain organ approach has been used.
- rTMS is painless and side-effect free. The rTMS field is evolving quickly with portable home-based devices on the horizon.
- The UCLA researchers anticipated that “that rTMS treatment will significantly improve many of the symptoms of ME/CFS.” and hope that it lays the foundation for a large placebo controlled, double-blinded trial.
- The 20-person trial will begin shortly and is open to women with ME/CFS
rTMS mostly stimulates of the surface of the brain cortex but has effects far beyond that. The special 3D cameras they use are able to very precisely target areas.
TMS can also be used to study the brain, and that’s how it’s mostly been used in ME/CFS. Several ME/CFS studies in the early to mid 2000s found reduced motor cortex excitability. That suggested that at least part of the fatigue in ME/CFS was “central”; i.e. it emanated from the brain, and that ME/CFS brains may be having difficulty activating the muscles during exercise.
Except for a small Japanese case series, and a small open label trial, rTMS has been little studied as a treatment option in ME/CFS. The case series, though, concluded that, “In most of the patients, treatment resulted in an improvement of fatigue symptoms”, and the open label trial found that both people with mild/moderate or severe cases of ME/CFS significantly benefitted. It called rTMS “a novel therapeutic intervention for ME patients” and concluded that:
“rTMS can improve fatigue symptom in ME patients regardless of (the )baseline severity of (the) fatigue symptoms”.
I’ve also been in touch with a retired pharmacologist who, after numerous unsuccessful trials (minocycline, Celebrex, Mirapex, SAME, provigil, dextroamphetamine, nexavir, ribose, Dr. Enlander’s protocol, n acetylcysteine, acetyl l-carnitine, vitamin B 12(oral), Trental, Transcranial direct-current stimulation, NADH), found that rTMS twice markedly improved his fatigue, exercise intolerance and mental clarity. (The third attempt, however, failed.)
rTMS has been better assessed in fibromyalgia. With 7/10 studies with positive results, the outcomes have generally been good. Summing up the field is difficult as the degree, target and duration of the stimulation can change from study to study. Researchers are still learning about optimal stimulation rates and optimal stimulation targets for different diseases.
A recent dorsolateral prefrontal cortex study, however, found that the pain levels of FM patients dropped dramatically and stayed reduced for six months
The ME/CFS study includes fifteen women with ME/CFS who will receive 20 rTMS sessions.
It also comes with a new and potentially quite significant twist. Past studies have used the rTMS to stimulate one part of the brain, but in a effort to produce a synergistic effect, the study is targeting two parts of the brain. Calling it a new protocol for UCLA, Dr. Leuchter said the ME/CFS study will target both the motor cortex and the prefrontal cortex.
Using a process called “inhibitory stimulation”, the motor cortex will be stimulated to turn down activity in the limbic system. The limbic system – which includes the amygdala – adds feelings of “unpleasantness” to the sensations we experience and activates the fight/flight system. (Unpleasantness is a rather mild word for the suffering that the limbic system can impose, but so be it). Suffice it to say that if the stimulation works your unpleasant sensations might still be there but they would be far less intrusive.
Leuchter believes, as others do, that hyperactivated limbic systems may be causing the problems with pain, lights, sounds and odors that often show up in ME/CFS, FM and related disorders.
While the UCLA group attempts to tamp down the activity of the limbic system, they’ll be trying to boost the activity of its antagonist – the dorsolateral prefrontal cortex (dPFC). The prefrontal cortex is tasked with reining in the fear-driven messages coming from the more primitive limbic system. It’s also involved in the “motor planning” that must take place before we can move, as well as cognition, organizing, decision-making, memory, etc. Boosting the dPFC could also result in reduced pain and fatigue, improved cognition, planning, memory, etc.
- See the blog below for a fuller explanation of the limbic system/prefrontal cortex interaction
The study doesn’t end there. Electroencephalograms (EEGs) taken before, during, and after the study will also be used to assess if the rTMS changes patterns of activity in the brain.
Corlier and Leuchter reported:
“We anticipate that rTMS treatment will significantly improve many of the symptoms of ME/CFS. Positive results from this study will provide proof-of-concept evidence for a novel rTMS treatment approach for ME/CFS to be validated in a future double-blind, randomized control trial.”
They hope to begin the study soon and are looking for participants. I’m trying to find out the correct contact information the UCLA TMS Clinical and Research Service might work.
That would be a nice step forward for a disease which has had all too few clinical trials.
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