Discovery raises possibility of new medication for Alzheimer's,
Parkinson's
OHSU study reveals that synthetic compound regulates gene implicated in neurodegenerative diseases

Date:
August 12, 2021
Source:
Oregon Health & Science University
Summary:
Researchers have for the first time demonstrated it's possible
to use a synthetic thyroid hormone to regulate a gene implicated
in neurodegenerative diseases like Alzheimer's, Parkinson's and
multiple sclerosis.



FULL STORY ========================================================================== Researchers from Oregon Health & Science University have for the first
time demonstrated it's possible to use a synthetic thyroid hormone to
regulate a gene implicated in neurodegenerative diseases like Alzheimer's, Parkinson's and multiple sclerosis.


==========================================================================
The findings from tests in cells and mice, published today in the
journal Cell Chemical Biology, raise the possibility of development of
new medication to treat debilitating diseases.

"This is the first example reported that shows it's possible to increase
the expression of the TREM2 gene in a way that will lead to healing in
certain diseases," said senior author Tom Scanlan, Ph.D., professor
of physiology and pharmacology in the OHSU School of Medicine. "This
will generate a lot of excitement." The paper's first author is Skylar
J. Ferrara, Ph.D., a postdoctoral fellow in the OHSU School of Medicine's chemical physiology and biochemistry department.

The discovery builds on a 2013 publication linking genetic variants of
TREM2 to risk of Alzheimer's disease.

The new research from OHSU builds on that work by showing that it's
possible to turn on TREM2 expression and the TREM2 pathway using
a compound originally developed more than two decades ago to lower
cholesterol.



========================================================================== Researchers administered an analog of the compound that penetrates into
the central nervous system of mice. They discovered they were able to
increase the expression of TREM2 and reduce damage to myelin. Myelin
is the insulation-like protective sheath covering nerve fibers that's
damaged in disorders like multiple sclerosis.

The pathway activated by the TREM2 gene is also implicated in
neurodegenerative diseases, including Alzheimer's and Parkinson's.

"TREM2 is a receptor," Scanlan said. "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's going to lead
to a therapeutic effect in most neurodegenerative diseases." Joseph
Quinn, M.D., professor of neurology in the OHSU School of Medicine,
who treats patients with Parkinson's and Alzheimer's, said the findings
are promising. Quinn wasn't involved in the research.

"TREM2 is a viable 'target' for treatment in Alzheimer's disease,
based on genetics and other studies," Quinn said. "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 analogs, is already licensed by an
OHSU spinoff company to conduct clinical trials for central nervous
system diseases, including multiple sclerosis. In contrast to other
basic science discoveries in mice, Scanlan said 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 possibility of doing clinical trials is not millions
of miles away," Scanlan said. "It would be an achievable thing." ========================================================================== Story Source: Materials provided by
Oregon_Health_&_Science_University. Original written by Erik
Robinson. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Skylar J. Ferrara, Priya Chaudhary, Margaret J. DeBell, Gail
Marracci,
Hannah Miller, Evan Calkins, Edvinas Pocius, Brooke A. Napier,
Ben Emery, Dennis Bourdette, Thomas S. Scanlan. TREM2 is thyroid
hormone regulated making the TREM2 pathway druggable with ligands
for thyroid hormone receptor. Cell Chemical Biology, 2021; DOI:
10.1016/ j.chembiol.2021.07.014 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210812092728.htm

--- up 13 weeks, 6 days, 22 hours, 45 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)