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A unique type of muscle fiber found in the extraocular muscles has been shown to be resistant against the disease ALS, and has been shown to even increase in proportion to compensate when other types of muscle fibers decrease in proportion. This is shown by research by researchers at Umeå University and University Hospital of Umeå. The finding could mean hope of eventually finding new treatment strategies for slowing down the dreaded disease.
“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.
When other types of muscle fibers atrophies in ALS patients so that they lose more of their function, it is a fact that most patients with ALS have the function of the extraocular muscles intact even late in the course of the disease. This is despite the fact that several extraocular muscles are required for the eye to move and function properly. Researchers in Umeå have found a possible explanation for this phenomenon. A unique type of muscle fiber in the extraocular muscles seems to not only be resistant in ALS, but the unique type of muscle fiber even increases in proportion in relation to other muscle fibers that are not as resistant in ALS.
Researchers have previously been able to show that the extraocular muscles have been only mildly affected in ALS, however, the researchers in Umeå have taken the research one step further by investigating this unique type of muscle fiber found in the extraocular muscles that is not found in the muscles in arms and legs. By using specific antibodies that attach to different types of proteins, the researchers have managed to map three large groups of muscle fibers in the extraocular muscles and investigate changes in distribution patterns in ALS. The researchers could show that a large group of muscle fibers in the innermost part of the extraocular muscles, which have a muscle fiber composition which is similar to the muscle fibers in the arms and legs, decrease in proportion in ALS.
Instead, these muscle fibers that are affected in ALS are replaced by the type of muscle fiber that is unique to the extraocular muscles. These unique muscle fibers are not only spared in ALS, but they also increase in proportion. This process could possibly be an important factor in ensuring that the extraocular muscles continue to function even late in the course of the disease, when other striated muscles in the body atrophies and loses their function. However, the extraocular muscles depend on signals from nerve cells to be activated. The findings about these unique muscle fibers being spared in ALS, and that the innervation between these unique type of muscle fibers and the nerve cells that activate these muscle fibers is preserved, could thus also indicate that the nerve cells that control these unique muscle fibers might also be more resistant to the pathological process in ALS.
“The findings provides 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.
Amyotrophic lateral sclerosis, ALS, is a severe neurodegenerative disease that leads to the loss of nerve cells in the brain and spinal cord that controls striated muscles used in voluntary movements. The disease is fatal, with a survival that varies between several months to several years from the time of symtom onset. Patients with ALS can be stratified into spinal-onset ALS, where symptoms starts in an arm or a leg, and bulbar-onset ALS, where symptoms starts in the head and neck region. In Sweden, about 200 people are diagnosed with ALS each year.
Arvin Behzadi
PhD student and MD, Department of Clinical Sciences, Neurosciences, Umeå University
Phone: +46723759814
E-mail: arvin.behzadi@umu.se
Anton Tjust
Researcher and resident physician in clinical neurophysiologyDepartment of Clinical Sciences, Neurosciences, Umeå University
E-mail: anton.tjust@umu.se
Fatima Pedrosa Domellöf
Professor and Chief Physician in Ophthalmology
Department of Clinical Sciences, Ophthalmology, Umeå University
fatima.pedrosa-domellof@umu.se
The study is published in the scientific journal Investigative Ophtalmology & Visual Science.
Myofiber Type Shift in Extraocular Muscles in Amyotrophic Lateral Sclerosis
Arvin Behzadi; Anton Erik Tjust; Jing-Xia Liu; Peter Munch Andersen; Thomas Brännström; Fatima Pedrosa Domellöf
Investigative Ophthalmology & Visual Science May 2023, Vol.64, 15.
https://doi.org/10.1167/iovs.64.5.15
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