Science & Medicine: Alzheimer's and the inflammatory trigger
A UT Health Science Center San Antonio researcher has discovered something really interesting about Alzheimer’s disease.
Bess Frost, PhD, an associate professor in Cell Systems and Anatomy, is a scientist at the university’s Barshop Institute for Aging and Longevity Studies and its Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. Her team recently discovered that an inflammatory trigger, like one present during viral infections, is elevated in Alzheimer’s — but this inflammatory trigger isn’t from our time.
“So over the course of human evolution, our genome has accumulated a lot of viral sequences. You can think of these as viral sequences that your great, great, great, great — extend the greats all the way to the beginning — were infected with, and these viruses now live in our genome as regular sequences,” Frost said. “It’s just part of who we are now.”
But something happens in Alzheimer’s disease, Frost explained.
“These viruses — that are part of our normal DNA now — we think that they're making the body think that there's a viral infection when, really, it's just an expression of these genes now that we got a long time ago.”
Our bamboozled immune systems then try to fight off our ancestors’ ancient virus, causing inflammation in the brain.
Frost theorized that if our immune systems think they’re fighting a virus, perhaps simple antiviral medications might be an effective treatment.
“These endogenous retroviruses in the human genome are so similar to viruses, in general, we think that we can repurpose antiviral medications to stop the endogenous retrovirus activation and thus lessen neurodegeneration,” she explained.
So Frost designed a drug trial in a small group of Alzheimer's patients. The medicine being tested is called 3TC. It’s FDA approved for HIV and hepatitis b. The participants took the medication for six months, and Frost’s team is now analyzing the data. If they determine the medication kept neurodegeneration steady over the six month period of the trial, that would be a "great" outcome, according to Frost.
“I think that would...definitely provide strong rationale for moving on to the next phase of the study, where we would have a larger group of participants as well as a placebo control,” Frost said.
The stakes are high. Two new medications for Alzheimer's have been approved recently, but Frost said they don’t “move the needle” much in terms of patient function. They also require people to come into clinics for infusions, making them inconvenient. They're also prohibitively expensive for most people.
The medication Frost’s team is studying — 3TC — is a once-a-day pill patients can take at home. It’s been in use as an antiviral since the 1990s and is now generic with the associated affordable price tag. It will take more time and study to determine how effective it is for this purpose, but the possibilities are exciting.
Frost is also hopeful that her findings will apply to other neurodegenerative diseases that occur when toxic deposits of a protein called tau clump together in the brain, collectively known as tauopathies. Based on her initial research on endogenous retroviruses in the brain, labs across the country are studying antiviral medications in Alzheimer’s as well as another tauopathy, progressive supranuclear palsy.
Science & Medicine is a collaboration between TPR and The University of Texas Health Science Center at San Antonio, about how scientific discovery in San Antonio advances the way medicine is practiced everywhere.