CC023 mice reveal how ALS can develop after viral infections

A large multidisciplinary study, lead by scientists at Texas A&M University, has made a new discovery that could change how amyotrophic lateral sclerosis (ALS) is studied and treated.

The researchers identified a specific mouse strain, known as CC023, that responds to a viral infection in a way that closely resembles ALS in humans. The finding reinforces a long-standing theory that viral infections may trigger permanent neurological damage long after the infection itself has cleared, opening up new techniques for drug discovery.

“This is exciting because this is the first animal model that affirms the long-standing theory that a virus can trigger permanent neurological damage or disease – like ALS – long after the infection itself occurred,” said Candice Brinkmeyer-Langford, a neurogenerative disease expert with the Texas A&M University School of Public Health.

A new platform for early intervention

The CC023 mouse strain offers researchers a rare opportunity to study the earliest biological changes that occur after infection but before irreversible motor neuron loss. Brinkmeyer-Langford said the model provides a unique “test track” for identifying biomarkers that appear following infection and signal the onset of ALS-like disease.

These biomarkers could prove critical for drug development, allowing therapies to be tested at earlier stages when they are more likely to slow or prevent disease progression. This is particularly significant for sporadic ALS, which accounts for more than 90 percent of cases and has no clear genetic inheritance pattern.

How the study worked

The study examined how five genetically diverse mouse strains responded to infection with Theiler’s murine encephalomyelitis virus (TMEV). The animals were monitored through acute, subacute and chronic phases of infection.

Researchers tracked spinal cord inflammation, paralysis and other physical symptoms over time, compared immune responses between strains and measured viral levels to determine whether more virus led to greater damage.

Four defining findings

The researchers reported four key outcomes:

• Early nerve damage: All mouse strains showed lumbar spinal cord damage within two weeks, with some displaying illness as early as four days after infection.
• Permanent muscle loss: Even after the virus was cleared from the spinal cord, CC023 mice experienced lasting muscle wasting.
• ALS-like symptoms: CC023 mice developed physical signs and spinal lesions closely resembling those seen in humans with ALS.
• Immune response timing: Immune cells were highly active during the initial infection but ceased activity once the virus was eliminated, even though neurological damage persisted.

Implications for drug discovery

These findings suggest that ALS-like disease can emerge from a short-lived viral infection followed by a sustained and damaging immune response. This shifts attention towards immune signalling, inflammation and post-viral mechanisms as potential drug targets rather than focusing solely on motor neurons.

The CC023 model could improve preclinical testing by providing a system that more accurately reflects sporadic ALS in humans. It may also help researchers identify which patients are most likely to benefit from specific therapies based on genetic susceptibility.

“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 lasting, damaging reaction in susceptible individuals,” said Brinkmeyer-Langford