Heterogeneity in motoneuron disease.
Recently, mutations in several genes have been identified as primary causes for the degeneration of motoneurons and their axons. Strikingly, mutations in the same genes were associated with clinically different motoneuron syndromes. The identity of these genes also shed light on the mechanisms of motoneuron degeneration and revealed that overlapping motoneuron phenotypes might be caused by heterogeneous molecular mechanisms. Overall, these findings have challenged the diagnostic classification system set by clinical judgement and triggered the notion of heterogeneity in motoneuron disease. It will now be especially relevant to identify the mechanisms and principles that motoneuron diseases have in common, as this will allow us to identify the most relevant therapeutic targets. On the other hand, heterogeneity in motoneuron disease also implies that finding a monotherapy cure for motoneuron disease will be challenging and that pre-clinical testing of therapeutic targets should not be limited to a single animal model.
Lambrechts
Diether
D
The Center for Transgene Technology and Gene Therapy, K.U. Leuven, B-3000, Leuven, Belgium.
Robberecht
Wim
W
Carmeliet
Peter
P
D000818:Animals; D018740:Genetic Heterogeneity; D006801:Humans; D008954:Models, Biological; D016472:Motor Neuron Disease / Q000145:classification / Q000235:genetics*; D009154:Mutation