New mechanism found to slow onset of ALS

Hopkins researchers have recently made a discovery that have implications in the treatment for amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig’s disease.

ALS weakens the neuromuscular system by targeting gray matter motor neurons in the brain and on the sides of the spinal cord, replacing healthy nerves with scarred tissue. Over time, as these neurons disappear, the muscles they control shrink and atrophy from underuse. As a result, those who suffer from the condition exhibit a trend of decreasing muscle mass, and in the last stages, paralysis and death.

Johns Hopkins researchers have high hopes that they have discovered a possible mechanism to slow the onset of the disease. Findings that were published in Nature Neuroscience concern a very specific group of nervous system cells known as oligodendrocytes and their role in the myelination of neurons.

Oligodendrocytes insulate neurons with myelin, a substance that helps to increase the speed of electrical impulse propagated down the length of a neuron. They also provide metabolic assistance to neurons. Scientists now have reason to believe that the previously overlooked oligodendrocytes may provide key insight to the workings and development of ALS.

To study the disease, researchers bred mice with the same gene mutation that causes ALS in humans. They found that, in such mice, striking changes occurred in the oligodendrocytes partnered with motor neurons, which are in charge of movement.

These specific oligodendrocytes exhibited drastically shorter life spans and died off at high rates. Oligodendrocytes that were regenerated in their place were much weaker and unhealthier than their predecessors. In fact, they were stunted in growth and failed to reach full maturity, resulting in progressive demyelination of and decreasing nutrient transfer to motor neurons. This degradation of gray matter oligodendrocytes can be physically observed before ALS symptoms of muscle atrophy manifest in mice as well as in humans.

Researchers discovered, however, that suppressing the ALS-causing gene mutation greatly delayed the appearance of the physical symptoms of Lou Gehrig’s disease in the laboratory mice, thereby increasing their lifespan by several months. While several months may seem like a short period of time to us, it is very long for lab mice. Scientists hope that the same principle of gene suppression can be applied for humans suffering from the condition.

Until now, researchers in the field had not fully appreciated the role of oligodendrocytes in the health and survival of motor neurons. This new knowledge will help narrow research focus to these specific cells and hopefully serve as a foundation for future research regarding the investigation and treatment of Lou Gehrig’s disease.

However, because of the novelty of these findings, very little is known about the exact role of abnormal myelination in the disease. Still, scientists remain hopeful and look towards a continuation of this type of research.

Robert Kalb, a neurologist at the Philadelphia VA Medical Center, was able to offer predictions for the next step in this breakthrough research. He alludes to multiple sclerosis (MS), a disease of the brain in which the loss of myelin plays a critical role.

“Some groups will administer MS drugs to mouse models of ALS and see if this leads to improvement in the disease. It so, it would probably go to human clinical trials,” he wrote in an email to The News-Letter. Hopefully, researchers in the battle against Lou Gehrig’s disease will find success in these endeavors. Meanwhile, teams across the nation are still investigating possible mechanisms involved in the development of ALS and continue to make progress towards a cure.