New ME/CFS Research Finding: Protein Disrupts Cells' Energy in Mitochondria

In a series of surprising twists worthy of a thriller and a bit of serendipity, researchers from the NIH's Heart, Lung, and Blood Institute (NHLBI) were studying genetic mutations in a family with cancer and ended up making an important discovery in ME/CFS research. It's a fascinating story, with excellent repercussions for ME/CFS patients, possibly leading to clinical trials in the near future!

One member of the family being studied, a 38-year-old woman, had a genetic mutation associated with the cancer that ran in her family. However, this woman (and none of her family members) had experienced worsening fatigue since she got mono (aka glandular fever) at the age of 16, including an inability to exercise. Sound familiar? As often happens, she'd never been diagnosed with ME/CFS, but clearly, she had all the hallmarks of our disease.

Rough outline of what these researchers discovered:

• Looking for genetic mutations responsible for cancer, they found a mutation in gene TP53. It was causing very high levels of a protein called WASF3 in the woman's samples but not in her siblings.
• The researchers did a literature search of WASF3, and guess what popped up? A little-known ME/CFS study, part of an effort by top ME/CFS researcher Suzanne Vernon, from 2011. She and her team had identified 227 patients with ME/CFS who were thoroughly examined and tested by top ME/CFS experts, creating an enormous set of data (which makes me wonder why the NIH ignored this fabulous set of samples and data when they recently published their "breakthrough" study of a measly 17 patients). The team published a paper that identified eleven different genes that were different in ME/CFS patients versus controls and specifically mentioned WASF3 as possibly being involved in the mechanism of fatigue and exercise intolerance.
• Finding that obscure paper, the NHLBI researchers kept digging and assessed other markers in the woman they were studying, compared to that 2011 ME/CFS paper.
• They also kept digging into the role of WASF3 and the effects when levels are high, as they were in both this woman and the ME/CFS patients studied.
• The researchers found that her muscle tissues had a lower oxygen consumption rate and reduced energy production.
• Next, they used RNA to reduce WASF3 levels in both her cells and healthy controls, and they saw mitochondrial (the energy engines in our cells) function improve across the board.
• Then the researchers produced mice with high WASF3 levels, and guess what? Their exercise capacity and ability to recover was significantly decreased (again, sound familiar?).
• They discovered that high WASF3 levels also causes high Endoplasmic Reticulum (ER) Stress Response. I know that's a mouthful, so let's just call it ER stress, as they do. This is important because high ER stress also occurs in other diseases.

The bottom line:  

These researchers studying cancer have found a new mitochrondrial abnormality that helps to explain not only fatigue in ME/CFS but also our characteristic exercise intolerance/post-exertional malaise. Even better: ER stress is a factor in other diseases, so there are already studies to look at supplements and medications to reduce it. This research team now wants to follow-up with possible clinical trials to try some of these treatments for ME/CFS specifically. And, of course, there's the fact that a whole new team of researchers are now fascinated by the complexities of ME/CFS and motivated to keep digging.

Here is the paper published last year by this team on WASF3 and ME/CFS. And, again, the 2011 paper on 11 genetic abnormalities in ME/CFS that helped them to connect the dots. 

To understand all of this, I read an excellent, easy-to-understand article in Science about the new study. And, as always, I relied heavily on Cort Johnson of Health Rising who worked his usual magic to make this complex series of events and scientific studies understandable. You can read Cort's article here (his sidebar, The Gist, is always helpful for a summary).

Exciting news! 

The fact that the research team is already planning clinical studies gives me hope.

What are your thoughts on these new study findings?

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