ALS Researchers Focus on Eye, Limb Muscles for Clues to the Disease

Amyotrophic lateral sclerosis (ALS) severely burdens skeletal muscles, while eye muscles remain far less affected. Vahid M. Harandi, a doctoral student at Umea University in Sweden, and his colleagues are focusing on the specific proteins involved in both areas’ response to ALS in an effort to better understand the pathophysiology of the disease from a muscle perspective.

ALS, a progressive neurodegenerative disease, is characterized by the accumulation of protein aggregates, or clumps, that affect the function of motor neurons, leading to progressive muscle weakness and paralysis due to the loss of these neurons in the brain and spinal cord. According to the National Institute of Neurological Disorders and Stroke, more than 12,000 people in the U.S. are diagnosed with ALS and a large proportion of people with ALS die from respiratory failure.

“ALS has traditionally been considered as primarily a motor neuron disease. However, accumulating data indicates that loss of contact between the nerve axons and the muscle fibers occurs early, long before the death of motor neurons,” Harandi, who is developing the research in the Department of Integrative Medical Biology and the Department of Clinical Sciences, Ophthalmology, said in a news release.

“This means that muscle fibers may be what’s initiating the motor neuron degeneration. These findings have led to a changing focus in ALS research from motor neurons alone to also include the muscle fibers and the neuromuscular junctions,” he added.

The researchers are specifically looking into the expression and distribution in limb and eye muscles of neurotrophic factors, secreted proteins that are able to stop apoptosis and enhance neuronal function, and Wnt proteins, known to be involved in a multitude of cellular and development processes. Alterations in both have been connected to several neuromuscular and neurological diseases, such as ALS.

“What we found were intrinsic differences between limb and eye muscles regarding expression of certain signal proteins involved in the development and vitality of neurons,” explained the researcher. “These differences, together with the fact that the neuromuscular junctions of eye muscles seem better able to preserve these signal proteins, known as neurotrophic factors, might play a role in the preservation of eye muscle function during ALS.”

Key findings from the research may ultimately explain how alterations in protein expression relate to ALS and aging and pave the way to new therapeutic approaches.