TREM2 regulation to prevent neurodegeneration is possible, study shows

Researchers at the Oregon Health and Science University (OHSU), US, have demonstrated that is it possible to use a synthetic thyroid hormone to regulate the TREM2 gene implicated in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and multiple sclerosis (MS). The findings from tests in cells and mice raise the possibility of development of new medication to treat debilitating diseases.

The discovery builds on a 2013 study linking genetic variants of TREM2 to risk of Alzheimer’s disease. The new research from OHSU builds on that work by showing that turning on TREM2 expression and the TREM2 pathway can be achieved by using a compound developed over two decades ago to lower cholesterol.

The researchers administered an analogue of the compound that penetrates the central nervous system (CNS) of mice. They discovered that they were able to increase the expression of TREM2 and reduce damage to myelin, the insulation-like protective sheath covering nerve fibres that is damaged in disorders like MS. The pathway activated by the TREM2 gene is also implicated in neurodegenerative diseases, including Alzheimer’s and Parkinson’s.

“TREM2 is a receptor,” commented senior author Tom Scanlan. “It senses damaged cellular debris from disease and responds in a healing, productive way. The thought is, if you can simply turn up its expression, then that is going to lead to a therapeutic effect in most neurodegenerative diseases.” 

The team hope that the findings will pave the way for future treatments for neurodegenerative diseases. “TREM2 is a viable ‘target’ for treatment in Alzheimer’s disease, based on genetics and other studies,” said Professor Joseph Quinn at the OHSU School of Medicine, who was not involved in the study. “This new report has important implications for testing a new therapeutic approach for Alzheimer’s, including raising the potential for developing a new medication to regulate TREM2.”

The synthetic thyroid hormone compound, known as sobetirome and similar analogues, is already licensed by an OHSU spinoff company to conduct clinical trials for CNS diseases, including MS. In contrast to other basic science discoveries in mice, Scanlan claimed that this latest discovery connects this class of compounds to Alzheimer’s, Parkinson’s and other neurodegenerative diseases, advancing the science that much closer to clinical trials in people with debilitating disease.  

The findings were published Cell Chemical Biology.