Researchers Explore Extraocular Muscles' Potential Defense Against ALS

Researchers from Umeå University and University Hospital of Umeå have discovered a distinct type of muscle fiber in the extraocular muscles that exhibits resistance against amyotrophic lateral sclerosis (ALS). Furthermore, when other muscle fiber types decrease in proportion, this unique fiber type demonstrates an increase to compensate. These significant findings have the potential to contribute to the development of novel treatment approaches aimed at slowing down the progression of ALS.

The research findings have been published in the journal Investigative Ophthalmology & Visual Science.

"You should be very careful about talking about breakthroughs in ALS research. We are far from a curative treatment. But these results still show that everything is not only deteriorating, but that the body can also utilize defensive strategies in a way that is hopeful for future research," says Arvin Behzadi, doctoral student at Umeå University and physician.

In individuals with ALS, while other muscle fibers experience atrophy and functional loss, the extraocular muscles remarkably maintain their functionality throughout the disease progression. Despite the requirement of multiple extraocular muscles for proper eye movement and function, ALS patients consistently retain intact extraocular muscle function even in later stages of the disease.

Researchers in Umeå have made a significant discovery that could potentially explain this phenomenon. They have identified a distinct type of muscle fiber within the extraocular muscles that not only exhibit resistance against ALS but also demonstrate an increase in proportion relative to less resistant muscle fibers affected by ALS.

Building upon previous findings indicating mild effects of ALS on the extraocular muscles, researchers in Umeå have delved deeper into their investigation. Specifically, they focused on examining a unique type of muscle fiber exclusive to the extraocular muscles, absent in the muscles of the arms and legs. By utilizing specific antibodies capable of binding to various protein types, the researchers successfully mapped three distinct clusters of muscle fibers within the extraocular muscles.

They also studied alterations in distribution patterns occurring in ALS. The results revealed a significant decrease in proportion of a substantial cluster of muscle fibers situated in the innermost region of the extraocular muscles, displaying a muscle fiber composition akin to that observed in the arms and legs.

In contrast, the muscle fibers affected by ALS undergo replacement with the distinctive type of muscle fiber found exclusively in the extraocular muscles. Remarkably, these unique muscle fibers not only remain unaffected by ALS but also exhibit an increase in proportion. This process potentially plays a vital role in enabling the continued functionality of the extraocular muscles, even in the later stages of the disease when other striated muscles in the body experience atrophy and loss of function. However, it is important to note that the activation of the extraocular muscles relies on signals from nerve cells.

The preservation of these exclusive muscle fibers in ALS, along with the undisturbed innervation between these muscle fibers and the nerve cells responsible for their activation, suggests the possibility that the nerve cells controlling these muscle fibers may possess greater resistance to the pathological processes associated with ALS.

"The findings provide a deeper understanding of the potential protective mechanisms that the body can harness against ALS. More research is needed to investigate exactly which protective mechanisms these unique muscle fibers and the nerve cells that control these muscle fibers can use, and whether these protective mechanisms could in any way be induced in other striated muscles and nerves in other regions of the body that is affected in ALS," says Arvin Behzadi.

Reference

Arvin Behzadi et al, Myofiber Type Shift in Extraocular Muscles in Amyotrophic Lateral Sclerosis, Investigative Opthalmology & Visual Science (2023). DOI: 10.1167/iovs.64.5.15