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.” How well they actually do this relative to the padding of their own budgets is a good question I might take up down the line, but you would think they might at least put some effort into writing plain-English summaries of technical material (medical and scientific research) in ways that educate and inform regular people.

But no.

Clear writing about CMT research, results, and the realistic possibilities for “treatments and cures” is exceedingly rare. I’m afraid a lot of the reason why is that a solid journalistic approach — pointed, probing questions and straight answers — would turn up less than epic stories of miracles 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.

No single cause — or cure for CMT

But the reality is, science proceeds slowly. Major breakthroughs that change millions of lives are very rare. And 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. 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.

Bring a "Mostly Dead" Book Back to Life as an Audiobook

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. I wrote about this back in June. 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.)

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 treatment using existing drugs (aldose reductase inhibitors) for diabetes. These drugs may be able to mitigate the nerve damage, 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 sometimes refered to as 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 Research:

🧪 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?

🔬 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

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