EPHA4 Gene Identified as Target for Treatment of ALS

Neurologists seeking a way to treat the fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS) have identified the EPHA4 (ephrin type-A receptor 4) gene as a likely target for drug or genomic therapy.

ALS is a fatal, rapidly progressive neurodegenerative disorder characterized by weakness, muscle atrophy, and spasticity due to the selective loss of both upper and lower motor neurons. ALS is the most common motor neuron disease, affecting more than 86,000 people worldwide with an average life expectancy of only three to five years from onset.

Several research groups have focused their attention on the EPHA4 gene. This gene encodes the ephrin type-A receptor 4 protein. The gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. The ephrin receptors are divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands.

In a paper published in the August 26, 2012, online edition of the journal Nature Medicine investigators at the University of Leuven (Belgium) showed that in a zebrafish ALS model EPHA4 expression inversely correlated with disease onset and survival, and loss-of-function mutations in EPHA4 were associated with long survival.

Other research groups are examining techniques for suppressing the activity of EPHA4. Of particular interest are developments in the possible application of siRNA (short interfering RNA) therapy for the inhibition of this gene. For example, RXi Pharmaceuticals Corporation (Westborough, MA, USA) is already at the product discovery phrase with RNAi-based therapeutics for ALS.

Related Links:
University of Leuven
RXi Pharmaceuticals Corporation