Good news on the CMT2 research front! The CMTA and HNF recently announced:
A team led by Dr. Stephan Züchner at the University of Miami has discovered a new type of Charcot-Marie-Tooth (CMT) disease that may be treatable with drugs already approved for other diseases. Züchner’s team, including Drs. Andrea Cortese, Grace Zhai, Adriana Rebelo and many others, found that mutations in the SORD gene cause an axonal form of CMT that is recessive. This study was substantially supported by the Inherited Neuropathies Consortium (INC) led by Dr. Shy in Iowa.CMTA: New, Potentially Treatable, Type of CMT Discovered
Published in Nature Genetics last month, the INC group’s findings are a big deal, and there is a really cool story from the University of Miami’s Miller School of Medicine about how the research team came together. Here’s what I understand to be the key facts in their discoveries.
The SORD gene allows your body to create an enzyme to convert sorbitol, a sugar alcohol, into fructose. Mutations to this gene can produce a recessive hereditary neuropathy that has now been identified, by this study, in “45 individuals from 38 families across multiple ancestries.” All of them carry a mutated “nonsense” variant in SORD which causes CMT2.
An interesting part of this study is its use of fruit flies to test the impact of similar genetic mutations. Researchers saw “synaptic degeneration and progressive motor impairment” in these flies, but normalizing their (and human patients’) sorbitol levels with existing drugs approved for use in India, China and Japan “dramatically ameliorated” the effects on motor nerves and eyes. The conclusion of the study was that its findings “establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes.”
This is a happy (and in other ways distressing) thing to read as the future peace and stability of many countries falls further into question and walking suddenly became much harder for me. Especially for a few days recently I ran into some new leg/knee/ankle challenges caused by whatever unknown subtype of CMT2 I presumably have. Over time it only gets worse, so the idea there might be a relatively simple treatment (if not for me, then for some people) is at first a positive thought but also a bit sad for how much more of a difference it would have made if known earlier. In the future, more people ought to benefit profoundly from research like this at an early age or even before they’re born.
Of course, that future very much depends on our societies remaining capable of both the goodwill and intellectual labour advanced research requires on the global stage. Consortiums like the Undiagnosed Disease Network (UDN), the Rare Diseases Clinical Research Network (RDCRN), and the INC (which is part of the RDCRN where the HNF is a member) are not products of conflict, isolation, fear, and distrust. They (and others around the world) are key parts of the international cooperation that has always fuelled medical advances for CMT and other diseases. We need to keep those lights on.