The Problem With Writing About CMT

I’ve been increasingly irritated lately by US-based, CMT-related non-profit organizations that seem to compete with each other for donations — supposedly they drive research for “treatments and cures.” Each registered charity tends to suggest it is doing the most vital work or has been at it the longest, and so on. It makes me think of divorced parents competing for “best parent” status with their kids, which is not what we, the “patients” or “community” want, nor should we relish the paternalism in our implied dependence on the procurers of possible cures.

To be honest, this kind of intra-charity competition makes me wonder things like, “What percentage of donations go into research for cures versus administrative costs and staff budgets?” It makes me wonder why basic, daily, self-help to cope with CMT is not more of a focus. I hope I can take up those questions here for research and writing in the future. But the one question that most regularly grinds my gears is what I want to touch on today: Why can’t we put greater effort into writing plain-English summaries of technical material (medical and scientific research) in ways that educate and inform regular people?

I started this blog because I was reading lots of printed newsletters and online articles about scientific and medical knowledge about CMT. I found most of that material very difficult to read, understand, and come away knowing I had learned something important with a high confidence of accuracy. And this is still my experience now.

Why can’t we put greater effort into writing plain-English summaries of technical material (medical and scientific research) in ways that educate and inform regular people?

Clear writing about CMT research, results, and the realistic possibilities for “treatments and cures” is exceedingly rare. I’m afraid the reason why that is so has a lot to do with the incompatibility of marketing and public relations with journalism. Pointed, probing questions and straight answers seldom lead to epic stories of miracle cures and wonder workers. It might at times embarrass big businesses and organizations that stand to profit from disease research and medicine, and they are accustomed (and prefer, as people do) to having their asses kissed. In the big money domain of commercial drug development, greed is the only real goad to bring curative and therapeutic products to market. That’s the crappy system we have, but it does better when it faces informed, probing questions and scrutiny. I’m not sure how much I can do here to play much of a critical and informative role, but I’ll try. And today I’ll focus that effort on the largely chimerical promise of a “cure” for the huge constellation of rare diseases lumped under the labels of Charcot-Marie-Tooth, neuromuscular atrophy, and neuropathy.

No single cause — or cure for CMT

The reality is, science proceeds slowly — and then all at once. Major breakthroughs that change millions of lives are very rare but do happen. Unfortunately, the nature of “CMT” is that no single cause, treatment or cure will ever exist for it. CMT is an umbrella of disease types and subtypes. These have not been completely identified or reduced to their genetic causes, but there appear to be hundreds. We know the causes are many and diverse, while the progression of the disease is, well, progressive in nature. It gets worse day by day, minute by minute. Nerves and muscles weaken and die. Regenerating, restoring, or otherwise regrowing lost muscle and dead nerves in aging people is a whole ‘nother field not touched by CMT research.

So, “Get used to pain!” is good advice. You won’t hear it from the mainstream CMT organizations. But seriously, it is good advice and there are people who specialize in it.

To The Pain - Running the stage
This movie has sooo many relevant lines.

(A sidenote: I am on the waitlist to see the folks connected with Dr. Douglas Zochodne‘s lab at the University of Alberta. He has written the book on nerve regeneration, so that will be interesting to get into — someday.)

Why is is so hard to be clear — about CMT?

As an example of what I’m griping about, take the stories coming out of Dr. Stephen Züchner’s research group and their discovery of a new genetic cause of a type of CMT2. Or distal hereditary motor neuropathy (dHMN). Or “SORD deficiency.” I wrote about this back in June 2020. Since then, all the US-based CMT-related non-profits have circulated mostly opaque internet and newsletter “content” about Züchner’s results. The single most informative piece I’ve found on it comes from the Muscular Dystrophy Association where they did a fine interview and let Züchner speak clearly in response to good (albeit general) questions. Thank you, Dr. Züchner!

I'll use small words so that you'll be sure to understand you warthog-faced  buffoon! | Princess bride, Good movies, Important life lessons
I told you…

Züchner thinks this type of CMT affects only 3,000 people in the US, by a conservative estimate. That is 0.00075% of the total US population.

Small steps for most of us, but huge for a few CMTers

Rather buried in this expert source material from Dr. Züchner is the major limiting factor in the scope of his discovery’s impact within the CMT community: Züchner thinks this type of CMT affects only 3,000 people in the US, by a conservative estimate. That is 0.00075% of the total US population. (For context, all types of CMT are thought to affect 0.15-0.25% of all Americans.) That is the single most important fact — to the CMT community — that should have been reported about this study, modest as it may be. The fruit of Züchner’s research will matter a great deal to a few thousand people and some particular sub-populations. (Amish people are thought to have an incidence as high as 3% of this type of CMT.)

Added 1 Feb. 2021: The glass half full take on this story stresses the guesstimate that there are about 60,000 people worldwide who have CMT or a related disease due to a SORD mutation, which is 10% of the total cases in these highly under-diagnosed rare (but not incredibly rare) diseases. That’s not nobody — it’s a lot of people, and their situation is likely to be one that can be improved a lot pretty easily.

Maybe a treatment — but not a cure

The second most important takeaway is that Züchner’s research does not point to “a CMT cure” but a possible (and very likely effective) treatment using existing drugs (aldose reductase inhibitors) for diabetes. These drugs may be able to mitigate the nerve damage from over-concentrations of sorbitol, especially when an early-life intervention is made. That will be huge for people with this type of CMT if their axonal degeneration can be curbed early and sustained throughout their life.

What the science all boils down to is this: A damaged SORD gene leads to elevated sorbitol which kills your nerves’ axons, causing axonal neuropathy.

Tell us how it works — in plain English

The third most important thing good science and medical reporting could do for the CMT community is explain the basic mechanisms at work and what the research actually reveals. Restated in plain language, Züchner’s lab has identified a type of (axonal) CMT2 caused by a mutation to the SORD gene which carries instructions for the creation of an enzyme (sorbitol dehydrogenase) to convert a sugar alcohol (sorbitol) into fructose (a sugar). (Sorbitol is in a class called polyols and is also a carbohydrate. Seems like a complex matter for organic and polymer chemistry experts — I am not one! If you are, please tell me more. 😅)

What the science all boils down to is this: A damaged SORD gene leads to elevated sorbitol which kills your nerves’ axons, causing axonal neuropathy.

The way nerves are damaged by excess sorbitol is not known, according to the Nature article linked above — which is why this CMT-related research has broader implications and importance for diabetes and neurology. It stands to help many people beyond the CMT community and advance knowledge in several areas of medicine and biology.

Good Questions for Future Posts

These are the questions I have about emerging research on SORD and CMT, that I hope to revisit with new knowledge in the future. If you would like to help with answers, corrections, or questions of your own and ideas for this blog, please do get in touch.

🧪 Symptoms and Diagnosis: Apart from identifying a SORD mutation to diagnose a person with this type of CMT2, Züchner has said elevated sorbitol levels in a blood test should flag it. Would this normally be missed or related to diabetes? Or perhaps there is a sorbitol level threshold low enough to not look like diabetes but high enough to slowly damage axons?

🤕 How the Nerve Damage is Done: If several dozen people of different ages with CMT2 from a SORD mutation can be assessed, will we get a good picture of disease’s range of effects over time? Do the effects include diabetes or any impact on the kidneys and eyes? (Answering my own question, apparently not. That and the general clinical expression is summarized here.)

💊 Treatments: What are the specific drugs that might be used to treat CMT2 rooted in a SORD mutation? Are there known side-effects, especially with long term use? (The answer seems to be “no” for Epalrestat and Sorbinil.) Would it be possible to eliminate all progression of nerve damage with an early intervention? What do these drugs tend to cost? Who makes them?

🍎 Dietary Impacts: Can dietary changes reduce human sorbitol production, help increase the availability of enzymes that break it down, or inhibit the production of sorbitol? (The missing enzyme that converts sorbitol to fructose is composed of a zinc ion and some amino acids. Similarly, the chemicals that inhibit the enzyme that converts sorbitol to glucose is common to many herbs and plants like basil and spinach.)

🔬 Relation to Other Diseases: How important is this new finding in CMT2 research to the understanding of diabetes, neuroaxonal dystrophy, and other diseases? Should CMT research be more interdisciplinary than it is currently? Is there work being done in other fields or for other diseases that might help understanding of CMT too? Would CMT be better understood and treated as a type of hereditary neuromuscular wasting disease (neuropathy)?‍

Did this post help you understand CMT and CMT research (or anything else) better? Do you value clear science and medical writing? Are you interested in writing that digs into these topics and questions? Let me know! 💭

Get Used to Disappointment
Dan Knauss

Dan Knauss

Hi, this is my CMT blog, and I wrote this article. You can read about me and my CMT story. Get in touch if you’d like; I’m always happy to answer questions about CMT and the medical system.

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