While the lack of efficacy of BDNF has been attributed to its poor pharmacokinetics and pharmacodynamics properties, a number of observations in both human as well as rodent models of ALS have suggested that one of the causes of the underlying pathology in ALS is not the lack of BDNF supply but rather a defect in downstream TrkB signaling. Here, BDNF is linked to amyotrophic lateral sclerosis.