Research Press Release

Genetic modifier of ALS onset and progression

Nature Medicine

August 27, 2012

A receptor that modifies the onset of Amyotrophic Lateral Sclerosis (ALS) and the survival of motor neurons is reported online this week in Nature Medicine.

In ALS, the onset of disease and rate of progression of paralysis are highly variable. It is thought that certain genes can influence this variability.

Wim Robberecht and colleagues find that the expression of EPHA4, a receptor previously shown to influence axon growth, inversely correlates with disease onset and survival in individuals with the disease. Mutations that disrupt the expression or function of EPHA4 are identified in two unrelated individuals with ALS that exhibit uncharacteristically long survival, suggesting loss of EPHA4 may be protective. In mice, expression of Epha4 is higher in motor neurons that are more prone to degenerate. Furthermore, genetic loss or pharmacological inhibition of Epha4 extends survival in rodent models of ALS. These findings suggest that Epha4 may influence motor neuron death, disease onset and progression of ALS, and may be targeted therapeutically.

DOI:10.1038/nm.2901 | Original article

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