Navigation Links
Scientists identify new gene that influences survival in ALS

WORCESTER, MA A team of scientists, including faculty at the University of Massachusetts Medical School (UMMS), have discovered a gene that influences survival time in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). The study, published today in Nature Medicine, describes how the loss of activity of a receptor called EphA4 substantially extends the lifespan of people with the disease. When coupled with a UMMS study published last month in Nature identifying a new ALS gene (profilin-1) that also works in conjunction with EphA4, these findings point to a new molecular pathway in neurons that is directly related to ALS susceptibility and severity.

"Taken together, these findings are particularly exciting because they suggest that suppression of EphA4 may be a new way to treat ALS," said Robert Brown, MD, DPhil, a co-author on the study and chair of neurology at UMass Medical School.

ALS is a progressive, neurodegenerative disorder affecting the motor neurons in the central nervous system. As motor neurons die, the brain's ability to send signals to the body's muscles is compromised. This leads to loss of voluntary muscle movement, paralysis and eventually respiratory failure. The cause of most cases of ALS is not known. Approximately 10 percent of cases are inherited. Though investigators at UMMS and elsewhere have identified several genes shown to cause inherited or familial ALS, almost 50 percent of these cases have an unknown genetic cause. There are no significant treatments for the disease.

Wim Robberecht, MD, PhD, lead investigator of the Nature Medicine study and a researcher at the University of Leuven in Belgium and the Vesalius Research Center, screened for genes in zebrafish that blunt the adverse effect of the ALS mutant gene SOD1. Through this process, his team identified EphA4 as an ALS modifier. Dr. Robberecht's team went on to show that when this gene is inactivated in mice with ALS, the mice live longer.

Dr. Robberecht then turned to UMass Medical School to confirm that turning off EphA4 in human ALS cells would slow the progression of the disease. Dr. Brown and his team identified two human ALS cases with mutations in the EphA4 gene which, like the zebrafish and the mice, had unusually long survival times. This suggests that blocking EphA4 in patients with ALS may be a potential therapeutic target in the future.

In an exciting, related development, a new ALS gene (profilin-1) identified last month by UMMS scientists works in conjunction with EphA4 in neurons to control outgrowth of motor nerve terminals. In effect, gene variants at both the top and the bottom of the same signaling pathway are shown to effect ALS progression. Together these discoveries highlight a new molecular pathway in neurons that is directly related to ALS susceptibility and severity and suggests that other components of the pathway may be implicated in ALS.

"It is exciting that these two studies identify the same pathway in ALS," said John Landers, PhD, associate professor of neurology and lead author of the PFN1 study. "Hopefully this discovery will accelerate efforts to finding a treatment for ALS."


Contact: Jim Fessenden
University of Massachusetts Medical School

Related biology news :

1. Northwestern scientists create chemical brain
2. Scientists quantify nanofiber health risk to workers
3. Scientists shed light on glowing materials
4. Triage for plants: NYBG scientists develop and test rapid species conservation assessment technique
5. Danger in the blood: U-M scientists show how antibiotic-resisting bacterial infections may form
6. Scientists uncover strategy able to dramatically reduce chemotherapys side effects
7. Scientists discover new type of virus responsible for a devastating disease in snakes
8. UF scientists find state record 87 eggs in largest python from Everglades
9. Scientists use light to tag and track genetic processes
10. Scripps Research Institute scientists show copper facilitates prion disease
11. Scientists use worms to unearth cancer drug targets
Post Your Comments:
(Date:10/29/2015)... Oct. 29, 2015 Today, LifeBEAM ... partnership with 2XU, a global leader in technical ... smart hat with advanced bio-sensing technology. The hat ... to monitor key biometrics to improve overall training ... the two companies will bring together the most advanced ...
(Date:10/26/2015)... PUNE, India , October 26, ... --> --> ... Forecasts 2015 to 2021 as well ... Analysis 2015-2019 research reports to its ... . ...
(Date:10/23/2015)... GOLETA, California , October 23, 2015 ... and SensoMotoric Instruments (SMI) announce a mobile plug and ... captured during interactive real-world tasks SensoMotoric Instruments ... of their established wearable solutions for eye tracking and ... behavior captured with SMI Eye Tracking Glasses 2w ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , November 25, 2015 ... Research Report is a professional and in-depth study ...      (Logo: ) , ... of the industry including definitions, classifications, applications and ... provided for the international markets including development trends, ...
(Date:11/24/2015)... Nov. 24, 2015 Cepheid (NASDAQ: CPHD ... at the following conference, and invited investors to participate ...      Tuesday, December 1, 2015 at 11.00 a.m. ...      Tuesday, December 1, 2015 at 11.00 a.m. ... New York, NY      Tuesday, December ...
(Date:11/24/2015)... , ... November 24, 2015 , ... ... of the year and one of the premier annual events for pharmaceutical manufacturing: ... from 8–11 November 2015, where ISPE hosted the largest number of attendees in ...
(Date:11/24/2015)... PA (PRWEB) , ... November 24, 2015 , ... This ... entrepreneurs at competitive events in five states to develop and pitch their BIG ideas ... projects from each state are competing for votes to win the title of SAP's ...
Breaking Biology Technology: