US researchers just discovered a novel gene associated with amyotrophic lateral sclerosis (ALS) that compromises motor neuron function in mice and zebrafish. The UBQLN4 genetic variant impairs nerve development through the excessive accumulation of beta-catenin, a realization that opens a new window for targeted treatment of ALS.
Amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s Disease refers to several variants of neurodegenerative disorders that impair neurons responsible for controlling voluntary muscle movement. ALS is considered a rare progressive disease, meaning it worsens over time, and affects roughly 2 out of 100,000 people worldwide. No effective cure to alleviate, halt or reverse its progression has been found to date, and the disease underwent increasing media attention in 2014 to promote public awareness.
It seems the spotlight paid off as a new study has just been released in this month’s issue of eLife which reports a novel gene involved in the onset and progression of ALS. The authors from the Northwestern University Feinberg School of Medicine were the first to link the UBQLN4 gene variant to the disease and describe its molecular mechanism of action.
“We know that many genes are involved in ALS and a major goal in the field is to identify as many of these genes as we can so we can uncover targets for treatment at the cellular level,” said lead author Brittany Edens.
The researchers tested the role of UBQLN4 in mice and zebrafish as a part of an ongoing joint investigation into mechanisms of ALS between two labs, funded by the National Institute of Health (NIH). The groups showed that the defects caused by UBQLN4 can be reversed with the drug quercetin, a beta-catenin signaling pathway inhibitor.
“We found that UBQLN4 gene variant interferes with a pathway involved in breaking down a certain protein called beta catenin, and the resulting accumulation of this protein leads to defects in the motor neuron structure. These defects likely make motor neurons vulnerable to progressive degeneration seen in ALS” added Edens.
It is important to note, however, that the results are preliminary and more research will have to be carried out before the drug can be tested in people with ALS. Nevertheless, for a disease which we had been trying to cure for decades, this represents a huge step forward. So keep those ice buckets pouring!
Learn more about ALS and it´s most famous patient Stephen Hawking in the video below:
By Luka Zupančič, MSc, University of Applied Sciences Technikum Vienna.