Scripps scientists to study several compounds with potential to improve QOL for ALS patients

Oct 9 2012

A team led by scientists at The Scripps Research Institute has been awarded $2.1 million by the Department of Defense Congressionally Directed Medical Research Programs to study several compounds with the potential to greatly improve the quality of life for those with amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease (named after the famed Yankee first baseman who died of the condition in 1941).

Philip LoGrasso, a professor on the Florida campus of Scripps Research, will be the principal investigator for the new two-year study, which also involves scientists from Columbia University.

"The potential impact a team effort like this could have on ALS patients may be tremendous, since there are currently no clinically beneficial, neuroprotective drugs for the disease," LoGrasso said. "We're hoping the compounds we're testing will lead to a drug to improve motor function and lengthen patients' lifespan through the prevention of motor neuron death."

LoGrasso and his Scripps Florida colleagues have already identified and validated a series of compounds that inhibit an enzyme called c-Jun N-terminal kinase (JNK, pronounced "junk") with proven neuroprotective effects in a variety of experimental models of human diseases, particularly Parkinson's disease.

JNK has been shown to play an important role in neuronal survival. As such, this kinase is a highly desirable target for drugs to treat neurodegenerative disorders.

Making the new study possible, LoGrasso said, are the cell and animal models of ALS produced by scientists at Columbia University. These models capture the hallmarks of this disease, including selective motor neuron degeneration, and many of the clinical features of the disease. "Given the success in neuroprotection that we've already shown with our proprietary JNK inhibitor in Parkinson's disease, we realized ALS was a perfect alternative candidate—primarily because Columbia had these models of the disease," LoGrasso said.

The team is also trying to develop new compounds that are highly selective for JNK3, a single isoform of JNK that is expressed only in the brain and the heart, thereby enabling tissue-specific inhibition and thus limiting many potential side effects.