TREM2 agonists for the preventative and therapeutic treatment of neugodegenerative disorders


Researchers at TGen have identified new potential preventative and therapeutic treatments for clinical management of Alzheimer’s disease and other neurodegenerative disorders with an immune neuorinflammatory component such as frontotemporal dementia, chronic traumatic encephalophathy, Down syndrome, or other diseases with an amyloid and/or tau neuropathy.  Through the development of a proprietary assay, TGen researchers targeted compounds for inhibiting amyloid and/or tau protein accumulation in the brain through the activation of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), specifically in microglial and myeloid cell brain tissue.  TREM2 forms a receptor-signaling complex with TYROBP (TYRO protein tyrosine kinase-binding protein, an ITAM-bearing transmembrane adaptor protein also known as DAP12), which regulates key signaling events involved in immune responses, differentiation of dendritic cells and osteoclasts, and phagocytic activity in microglia. 


Drugs currently approved by the U.S. Food and Drug Administration for Alzheimer’s disease do not prevent or reverse the disease and only provide modest symptomatic benefits.  A foundation for success through TGen’s inventive treatments has been found in studies where overexpression of TREM2 in AD transgenic mice decreased accumulation of amyloid plagues, neuroinflammation, loss of neurons and synapses, and increased spatial memory.  For patients diagnosed with very mild to moderate cognitive decline, TGen’s inventive treatment methods using compounds targeted to stimulate the phagocytic activity of the microglia may enhance the clearance of amyloid-β, apoptotic neurons, and other debris in the brain in order to prevent or slow disease progression. 


Patent Information:
For Information, Contact:
Katie Bray
Intellectual Property Counsel
The Translational Genomics Research Institute
Matt Huentelman
Isabelle Schrauwen
Wayne Jepsen