Enzyme May Lead to ALS Treatment


A drug similar to one now used to treat sepsis, an illness in which the bloodstream is overwhelmed with bacteria, holds promise as a treatment for amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease, per research published online in the October 19th Journal of Clinical Investigation.

In the study, Dr. Berislav Zlokovic, a neuroscientist at the University of Rochester Medical Center, and colleagues were able to extend the life span by 25% of mice with a severe form of ALS. The mice continued to show symptoms, but did not suffer from muscle degeneration as quickly and were better able to live more normal lives.

Amyotropic Lateral Sclerosis is a progressive disease that destroys motor-related neurons in the brain, brainstem and spinal cord. Cell death leads to paralysis, and death usually occurs within five years. Most patients with ALS are between the age of 40 and 70. There is currently no cure or treatment that can slow the progression of the disease.

The mice used in the study had a mutation in the gene known as superoxide dismutase 1, or SOD1. This gene plays an important role in keeping cells safe from free readicals. Most causes of ALS are unknown, but in about 3 to 4% of cases, an accumulation of mutated SOD1 plays a role.

Mutations to SOD1 can also weaken the natural barrier between the blood and the spinal cord, allowing toxic substances to enter. Motor neurons are then exposed to the biochemical products of hemoglobin, such as iron, which forms a reactive oxygen molecule that injures or destroys neurons.


The compound used was a form of an enzyme known as activated protein C or APC, used in the medication Xigris® by Eli Lilly. APC’s primary function is to prevent blood clotting. When given to the mice, it appeared to protect the neurons that are under attack in ALS. APC also appeared to lessen the activity of SOD1.

The drug can be given by injection, and appears generally safe. It can cause an increased risk of bleeding, so the researchers will hopefully be able to modify the compound to boost its chances of serving as a treatment for ALS.

The researchers warn that currently the drug has only been tested in mice, and there's no guarantee that it would have similar effects in humans. They plan to begin clinical trials on patients within the next five years.

Journal reference:

Zhong et al. Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells. Journal of Clinical Investigation, 2009;

Other resources include: The ALS Association, Xigris.com