A chemical cousin of a drug currently used to treat sepsis dramatically slows the progression of amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease, in mice. The results offer a bit of good news in efforts to develop a therapy to stop or slow the progression of a disease that generally kills its victims within just a few years.
In a paper published in the October 19 online edition of Journal of Clinical Investigation, scientists studied the use of a form of an enzyme known as activated protein C (APC) to slow the cell death that occurs in ALS.
"We were able to significantly extend the lifespan of mice with an aggressive form of ALS," said co-principal investigator Don W. Cleveland, PhD, professor and chair of the Department of Cellular and Molecular Medicine at UC San Diego, a widely recognized expert on ALS. "The compound also extended the length of time that the mice were able to function well despite showing some symptoms of the disease, and it reduced the pace of muscle wasting that is a hallmark of ALS."
While the investigators say that more research must be done before the enzyme is tested in people with the disease, they are encouraged that the work involves a compound that has already been proven to be safe and is currently given to patients via a common injection for another condition. The team hopes to test a treatment in patients within five years.
The work was done by a team of researchers from the University of Rochester Medical Center, led neuroscientist Berislav Zloikovic, MD, PhD; The Scripps Research Institute in La Jolla, including John Griffin, PhD, an expert on the APC enzyme; the University of Notre Dame; and a Rochester-based start-up biotech company, Socratech.
First authors of the paper were Zhihui Zhong of Rochester and post-doctoral associate Hristelina Ilieva with the Ludwig Institute at UC San Diego.
The researchers studied mice with a mutation in a gene called superoxide dismutase 1 (SOD1), which plays an important role in keeping cells safe from damaging molecules known as free radicals. While the cause of most cases of ALS is unknown, scientists do know that SOD1 plays a role in approximately three to four percent of cases - providing an opportunity to study the disease's initial steps, which occur long before key nerve cells appear sick or die. In addition, recent studies have suggested that the accumulation of mutant forms of SOD1 is linked to most cases of sporadic ALS.
Cell death is central to the symptoms of ALS, a chronic disorder of motor neurons in the brain, brainstem and spinal cord, which results in a progressive paralysis that generally kills individuals within five years of onset. Currently there is no cure or even a treatment that can effectively slow disease progression.