History provides an atlas for Ron Tjalkens’ research into neurodegenerative disorders like Parkinson’s, Alzheimer’s, and now long haul COVID-19.
When the COVID-19 pandemic began, Tjalkens had recently finished reading The Great Influenza by John Berry. In the influenza flu pandemic of 1918, he saw a historical precedent for long-term neurological effects in survivors of the SARS-CoV-2 virus. Exposure to the 1918 flu was linked to more than 1 million cases of encephalitis lethargica, a severe form of virally induced Parkinson’s that was memorably recorded in Oliver Sack’s book Awakenings. The H1N1 virus does not enter the brain, but it can cause so much inflammation in other organs and tissues that it triggers subsequent inflammation in the brain.
“If what happened a century ago is any sort of guidepost, then the neurological symptoms we’re seeing now with SARS-CoV-2 and the number of people that are getting it are going to result in an increase in neurological disease in the coming years,” Tjalkens said.
“Why do good glia go bad?”
Tjalkens is a leading scientist in the relatively young field of neuroimmunology. He studies the progression of neurodegenerative diseases like Parkinson’s and Alzheimer’s, and how neurotropic viruses—viruses that attack the nervous system—can trigger neurological disorders. The unifying question in his research program is a deceptively simple one: “Why do good glia go bad?”
Glial cells account for 90 percent of the brain. They provide the supportive environment that keeps nerve cells functioning, in part by responding to environmental stresses.
“The glia are always trying to keep nerve cells alive and healthy, but repeated environmental stresses over time, like changes in metabolism or repeated bouts of infection, or exposure to neurotoxins like heavy metals and pesticides can result in a chronic inflammatory state in the brain,” Tjalkens said. “We now know that this chronic inflammation is responsible for a whole series of pathological changes that lead ultimately to the demise of neurons.”
When neurons die, the brain loses control of movement, memory, and cognition, resulting in disorders like Parkinson’s and dementia. But neuronal death is the end stage of the disease, and Tjalkens seeks to understand the inflammation that leads to neurodegeneration. “If we can understand the molecular pathways underlying the change in glial cells, then we hopefully will uncover targets for therapy,” Tjalkens said.
A window into the brain
Prior to the pandemic, Tjalkens and virologists Tony Schountz and Rebekah Kading, as well as bacterial geneticist Richard Slayden, were working on preclinical drug trials for the neurotropic virus Western Equine Encephalitis. They quickly expanded their neurovirology work to include anti-inflammatory drug therapies for COVID-19. Colorado State University is one of a small number of universities in the world where this research can take place because it has both a Biosafety Level 3 laboratory and an animal model—the Syrian Golden Hamster—that can propagate the human virus.
“Viruses that can affect the brain are so dangerous because the inflammatory response elicited by viral infection can have long term effects on protein misfolding and dysfunction within the brain,” Tjalkens said.
Ultimately, Tjalkens hopes that studying viral infections like COVID-19 will provide a window into the mechanisms of neurodegenerative diseases like Parkinson’s and Alzheimer’s as well as therapies.
“This is critically important because there are currently zero drugs that alter or slow down the course of any neurodegenerative disease,” Tjalkens said. “All current treatments are only symptomatic. After a century of focusing on neurons, it’s not surprising that our therapies are no better than our understanding of the biology.”
One silver lining of the current pandemic could be a revolution in our understanding of and ability to treat neurodegeneration.
Tjalkens recommends these titles to learn more about the link between viral exposures and neurodegenerative diseases.
- The Great Influenza (2004), John M. Barry, history of the 1918 Spanish Flu pandemic
- Awakenings (1973), Oliver Sacks, recounts the life histories of those who had been victims of encephalitis lethargica in the 1920s following the 1918 influenza pandemic
- Spillover (2012), David Quammen, discusses the growing problem of zoonotic disease spillover from natural animal reservoirs to humans, with an uncanny prediction of the current coronavirus pandemic
- “Back to the future: lessons from past viral infections and the link with Parkinson’s disease” (2021), Eilis Dowd and Declan P. McKernan, a current review article of the literature on viral exposures and Parkinson’s disease, PubMed ID: 33953960