UAB Researchers Track New Pathway In Search For ALS Treatments

UAB research has shed new light into possible causes of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. In findings published in the July 25th issue of the Journal of Neuroscience, researchers point toward disruptions in messenger RNA that reduce a growth factor critical to the survival of motor neurons. ALS is marked by the rapid degradation and death of motor neurons.

July 24, 2007

BIRMINGHAM, Ala. – UAB research has shed new light into possible causes of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. In findings published in the July 25th issue of the Journal of Neuroscience, researchers point toward disruptions in messenger RNA that reduce a growth factor critical to the survival of motor neurons. ALS is marked by the rapid degradation and death of motor neurons.

Recent research has shown that decreased levels of vascular endothelial growth factor (VEGF) contribute to loss of motor neurons. In the current findings, Peter King, M.D., professor of neurology, and Liang Lu, M.D., assistant professor of neurology, show that a protein that protects RNA, known as HuR, is dysfunctional in some models of ALS. RNA is the main blueprint for production of proteins, including growth factors, and loss of RNA protection appears to correlate with a loss of VEGF.

“Something appears to be interfering with the function of HuR in these models of ALS, with a resulting drop in VEGF levels,” King said. “We’re seeing a disruption in the machinery that protects RNA.”

King says the cause of ALS remains unknown. It may be the result of genetic factors, environmental influences, infectious agents or all three.

“We do not understand the trigger, but studies in animal models for ALS show that VEGF RNA levels are drastically reduced from the early stages of the disease,” King said. “We believe this VEGF/HuR pathway is a promising avenue for further research.”

King is encouraged by recent advances in science’s understanding of ALS and suggests that the next 5-10 years will see remarkable progress in finding new treatments that may slow or halt the progression of the disease.

“An effective treatment or cure for ALS will not be possible until we understand the underlying cause or causes of the disease,” he said. “Therapies for ALS will only emerge from diligent efforts in the laboratory.”

King and Lu are clinician/scientists at UAB’s comprehensive ALS clinic, where they take insights gained from seeing ALS patients in clinic to their laboratories for evaluation.

“This clinical and basic science connection is essential for moving ALS research forward,” King said. “UAB is in a prime position to build on this connection due to our experiences in both clinic and laboratory.”

This research was funded by the National Institutes of Health.