Ascorbic Acid Effective in Mouse Model of CMT Disease

Not Another Earlobe

Previously, the Corpus Callosum asserted the premise that everything in the body has at least two purposes, except the earlobe.  A previous example was the finding that thyroid stimulating hormone inhibits the action of osteoclasts.  The fact is, the body works in mysterious ways.  You could interpret that as evidence for intelligent design; or, you could interpret it as evidence that humans are not smart enough to understand how their own bodies work.

Supernatural or not, the fact is, we keep discovering odd things about how the body works.  Somewhere, recently, I encountered an article that mentioned a finding about the role of erythropoietin and thrombopoietin in the developing brain. Now I can't find it, and it's driving me nuts. If I recall correctly, erythropoietin stimulates the growth of nerve cells in the developing brain, while thrombopoietin promotes nerve cell death. Erythropoietin got its name because the first function that was discovered was that of promoting the generation on new red blood cells. Thrombopoietin does the same thing for platelets.  Why nature would use the same molecules for one function in the bone marrow, and an entirely different function in the brain, remains a mystery. 

Since, I couldn't find the erythro/thrombropoietin article, I went looking for a different example. 

Now, we find that ascorbic acid (vitamin C) also has an effect upon neuronal survival, at least in mice with mutations of the PMP22 gene.  After this was discovered, it was assumed that the mechanism would have something to do with the well-know function of ascorbic acid, that of inactivating toxic molecules known as free radicals.  However, it now appears that it acts by reducing the expression of the PMP22 gene. 

Will wonders never cease?

The PMP22 gene codes for peripheral myelin protein 22, and is located on the short arm of chromosome 17.  In about half of patients with Charcot-Marie-Tooth disease (CMT), there is a extra copy of a region of the short arm of chromosome 17, which means there is an extra copy of the PMP22 gene.  This leads to "over-expression" of the gene, meaning that too much of the protein is made in persons with the disease. 

When mice with a similar problem are given a lot of vitamin C, it caused a 90% reduction in the amount of PMP22 RNA in one of the large peripheral nerves.  Those mice did not experience progression of the disease, and lived as long as normal mice. 

The original report was published in Nature Medicine: Passage E, Norreel JC, Noack-Fraissignes P, et al. Ascorbic acid treatment corrects the phenotype of Charcot-Marie-Tooth disease. Nature Medicine 10; 396-405.  It includes the usual disclaimer that mice are not people, so it is way too early to know how applicable this would be to a person with CMT.  Also, not all CMT patients have the same genetic abnormality, so even if it or a similar treatment does work for some humans, it might not work for all of them. 

Remember, vitamin C is not an earlobe.