TREM2 signaling as a biomarker and therapeutic target in ALS

2013 Pilot Project Read More


Principal Investigator: Matthew Harms (formerly WashU Neurology)
Co-Investigators: Timothy Miller (WashU Neurology), Marco Colonna (WashU Pathology & Immunology)


Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is caused by the relentless death of motor neurons in both the brain and spinal cord.  Degeneration of these neurons results in progressive paralysis of muscles and eventually leads to death when the ability to breathe is lost, typically in less than 5 years after the onset of disease.  The loss of neurons in ALS is accompanied by the proliferation and activation of microglia, which are cells of the innate immune response.  It was once thought that microglia were simply responding to neuronal degeneration, but mounting evidence from human and mouse studies demonstrate that microglia are active participants in the disease process.  However, their role is nuanced, as microglia can adopt either neuroprotective or neurotoxic phenotypes and can transition between these two states. Biasing microglia toward neuroprotection and away from neurotoxicity could potentially treat ALS and other neurodegenerative diseases where microglia are implicated.  Recently, the TREM2 receptor pathway has been identified as a potential regulator of the microglial phenotype.  This project will determine whether genetic variability in, or expression of, TREM2 pathway genes are a risk factor for ALS or influence disease.  Additionally, TREM2 levels will be genetically manipulated in a mouse model of ALS to determine if TREM2 signaling influences the severity or course of disease.

Updated July 2017

Hope Center Investigators

Matthew Harms

Timothy Miller


This pilot project is made possible by the Danforth Foundation Challenge, and The Hope Center Program on Protein Aggregation and Neurodegeneration (HPAN).

Danforth Challenge