A CHICKEN-OR-EGG QUESTION IN ALS TREATMENT

What goes first in the wasting disease known as amyotrophic lateral sclerosis: the muscles or the neurons that control them?

Most researchers have assumed that the neurons die off, starting the process of muscle wasting. But the story may not be so simple, according to a study by Chien-Ping Ko and colleagues in USC College.

Ko's group crossbred mice genetically predisposed to ALS with mice lacking myostatin, an "anti-growth" factor for muscle development. Knocking out the myostatin gene increases muscle mass two- to three-fold, creating super-muscular mice.

When these super-mice contracted ALS, they maintained strong muscles and normal body weight almost until the end, the study reports. In addition, their motor performance remained nearly normal, while control mice with ALS became severely impaired. Two of the female super-mice with ALS also lived 20 percent longer than expected.

More surprisingly, the super-mice also retained 38 percent more motor control neurons, or motoneurons, through the midpoint of their illness. The increased muscle mass appears to start a feedback mechanism that keeps the spinal cord healthier.

"These results indicate that myostatin deletion can slow weight loss, muscle wasting and motoneuron death as well as improve motor performance and life span [females only]," the study concluded.

Anti-myostatin therapy also may help human ALS patients, Ko suggested.

"At the very least, it can improve the quality of life," he said, adding that such therapy would be relatively easy. "You can enlarge skeletal muscle in a way that is less invasive to patients."

Ko's collaborators on the study were Yoshie Sugiura (a former research assistant professor at USC) and graduate students Sonia Ming-Yi Lin and Young-eun Yoo. The group is preparing its results for publication.

In a related presentation, Sugiura described the potential of testoterone therapy for improved motor performance in ALS mice.

And in a presentation on muscle improvements for patients with Parkinson's disease, a group led by Beth Ellen Fisher of the Department of Biokinesiology & Physical Therapy in the USC School of Dentistry, found that high intensity exercise not only improves motor performance but also appears to promote beneficial brain changes (neuroplasticity) in the motor cortex.

"If humans with Parkinson's disease are subject to neuroplasticity and behavioral recovery through high-intensity exercise, it is possible that exercise interventions may be designed to delay or reverse disease progression," Fisher's group concluded.

Ko poster presentation, Oct. 17, 2-3 p.m. (1-2 p.m. for Sugiura poster, 8:30-8:45 a.m. for Fisher presentation)
http://www.eurekalert.org/pub_releas...-ugp101306.php