EGFR inhibitor erlotinib delays disease progression but does not extend survival in the SOD1 mouse model of ALS

PLoS One. 2013 Apr 26;8(4):e62342. doi: 10.1371/journal.pone.0062342. Print 2013.


Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive paralysis due to motor neuron death. Several lines of published evidence suggested that inhibition of epidermal growth factor receptor (EGFR) signaling might protect neurons from degeneration. To test this hypothesis in vivo, we treated the SOD1 transgenic mouse model of ALS with erlotinib, an EGFR inhibitor clinically approved for oncology indications. Although erlotinib failed to extend ALS mouse survival it did provide a modest but significant delay in the onset of multiple behavioral measures of disease progression. However, given the lack of protection of motor neuron synapses and the lack of survival extension, the small benefits observed after erlotinib treatment appear purely symptomatic, with no modification of disease course.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Disease Progression*
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Humans
  • Longevity / drug effects
  • Mice
  • Mice, Transgenic
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / pathology
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Staining and Labeling
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Survival Analysis
  • Synapses / drug effects
  • Synapses / metabolism
  • Synapses / pathology
  • Time Factors


  • Biomarkers
  • Protein Kinase Inhibitors
  • Quinazolines
  • SOD1 protein, human
  • Erlotinib Hydrochloride
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • ErbB Receptors

Grant support

Genentech, Inc. funded this research. The study was funded by Genentech, Inc. through the employment (at the time of the study) of the authors. These authors contributed to all aspects of the study. The funders were involved in study design, data collection and analysis, decision to publish, and preparation of the manuscript.