Groundbreaking discovery reveals how viruses can trigger the development of ALS

A large multidisciplinary team led by researchers at Texas A&M University has made a potentially revolutionary discovery about the development of devastating motor neuron diseases such as amyotrophic lateral sclerosis (ALS).

The team identified a specific type of mouse, the CC023 strain, that responds to a viral infection in a manner remarkably similar to that of humans with ALS.

“This is exciting because this is the first animal model to affirm the long-standing theory that a virus can trigger permanent neurological damage or disease, such as ALS, long after infection has occurred.”

Candice Brinkmeyer-Langford, neurogenerative disease expert, Texas A&M University School of Public Health

The CC023 strain provides a unique “test lead” for scientists to identify early warning signs of ALS through biomarkers that appear after infection, he said. In addition, it could lead to tests and new treatments, especially for sporadic ALS, which represents more than 90% of cases and is not hereditary.

For their study, which was published in the Journal of Neuropathology & Experimental Neurology, the team used Theiler’s murine encephalomyelitis virus (TMEV) to infect five strains of genetically diverse animal models. They then assessed how the different strains’ unique DNA affected their responses to the virus during the acute, subacute and chronic phases of infection.

The researchers tracked changes over time and between different strains of mice using five methods:

Comparison of spinal cord inflammation between infected and healthy mice at different time points. Comparison of inflammation levels between the five strains of mice. To determine whether higher levels of inflammation were directly related to more paralysis and other serious physical symptoms. Measure the amount of virus present. To test whether higher amounts of the virus led to higher levels of spinal cord inflammation.

There were four key findings:

Early damage. In the first two weeks, all strains of mice showed damage to the nerves in the lumbar spine. Some strains showed signs of illness as early as four days after infection. Loss of muscle mass. During the prolonged phase of the disease, the virus was cleared from the spinal cord, but CC023 mice experienced permanent muscle atrophy. Similarities with ALS. CC023 mice showed physical symptoms and lesions very similar to those seen in humans with ALS. Immune response. While the mice’s immune cells were very active from the beginning to fight the virus, this activity stopped once the virus was eliminated.

In summary, the initial viral infection spread and infected the lumbar spinal cord early on, triggering an immune reaction, lesions, and signs of disease. The virus disappeared over time, but the lesions and clinical symptoms persisted, and in strain CC023 these signs resembled an ALS-like disease.

The bottom line, according to Brinkmeyer-Langford? Genetics matter.

“This study gives us a new way to understand the various types of damage caused by a viral infection to the spinal cord and its nerves and muscles, especially since we now know that the initial viral infection triggers a long-lasting harmful reaction in susceptible individuals,” he said.

This work was supported by the National Institute of Neurological Disorders and Stroke, the National Institute of Environmental Health Sciences, and a National Science Foundation Graduate Research Fellowship.

Others involved in the study were lead authors Koedi S. Lawley and Tae Wook Kang, as well as Raquel R. Rech, Aracely A. Perez Gomez, Katia Amstalden, Yava Jones-Hall, C. Jane Welsh and Colin R. Young, all from the College of Veterinary Medicine and Biomedical Sciences, along with Raymond Carroll, from the College of Arts and Sciences, and David W. Threadgill, from the College of Agriculture and Life Sciences, as well. like Moumita Karmakar of the University of Wisconsin-Madison.