Motor neuron disease is fatal and rapidly progressive neurodegenerative disorder of the human motor system. The disorder peaks in the late 50’s early 60’s and then declines after ager 80, an unusual statistic for a degenerative disease. In addition, familial forms of MND are increasing recognised, although the penetrance of the genotype is at best 80% by age 80. Further, the phenotype seems to be identical between different genotypes, at least in terms of the motor dysfunction, and “anticipation” has been reported. Importantly, most of the genetic mutations seem to disrupt vital cellular function such as DNA/RNA metabolism. So an important question to address is “why does it take 50 or 60 years for the disease to manifest in mutation carriers?”
In the must read review by Eisen and colleagues, the notion of a long pre-clinical period is raised with the possibility that ALS susceptibility is acquired in utero. Exposure to environmental and other factors may then trigger the devastating process. Such a construct has been suggested in other neurodegenerative diseases. Development of robust techniques to detect pre-clinical dysfunction, if any, could be the magic therapeutic bullet.
Eisen A, Kiernan M, Mitsumoto H, Swash M. Amyotrophic lateral sclerosis: a long preclinical period? J Neurol Neurosurg Psychiatry. 2014 Mar 19. doi: 10.1136/jnnp-2013-307135.
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