Researchers at Northwestern University have found that a combination of influenza drugs could reduce cognitive impairment and premature aging in people living with chronic infections. In a study published today in the journal Med, the team uncovered a previously unknown mechanism by which viruses like HIV drive cognitive decline over time even when effectively treated.
“We are not saying yet that people should take flu drugs to prevent cognitive decline,” explains Mohamed Abdel-Mohsen, PhD, associate professor of medicine in the division of infectious diseases at Northwestern University’s Feinberg School of Medicine. “We are saying that our findings open the door to testing whether this drug class, or better next-generation versions, could be repurposed for brain and aging-related complications.”
At least 25% of people living with HIV develop symptoms affecting their memory and thinking, even when the infection is effectively managed using antiretroviral therapy. Until now, the reason for it remained unclear.
Abdel-Mohsen’s team analyzed blood samples from more than 100 people in the AIDS Clinical Trials Group, all of which were infected with HIV and taking antiretroviral therapy. Based on clinical testing, the patients were separated in two groups, one having normal cognition and another cognitive impairment.
Results showed that those who developed cognitive impairment had reduced levels of glycans in their blood. These protective sugar molecules normally keep inflammation under control, but when they are degraded, inflammation becomes chronic and accelerates aging processes.
The researchers also found that glycan degradation was more pronounced among women in the study. While men saw changes in glycan levels evolve gradually and steadily over time, women experienced an acceleration around menopause.
“Before menopause, women show a slower loss of anti-inflammatory glycans and slower accumulation of pro-inflammatory glycans compared with men, but around menopause there is a rapid shift toward a more inflammatory glycan profile,” says Abdel-Mohsen.
In human immune cells and mouse models, a combination of two influenza drugs successfully preserved glycans and reduced inflammation, slowing down aging and protecting memory. The treatment was composed of oseltamivir, sold as Tamiflu, and an experimental drug. Both are glycan-based drugs belonging to the sialidase inhibitor drug class, which block an enzyme that the influenza virus relies on to replicate itself.
In future studies, the researchers will investigate whether glycans can serve as biomarkers of future cognitive decline, which could eventually lead to the development of predictive blood tests The team is also planning to further study and optimize potential treatment strategies based on the influenza drugs to prevent cognitive impairment.
“On the treatment side, we want to do more preclinical work to optimize the approach,” says Abdel-Mohsen. “Although some sialidase inhibitors are already used safely in people for influenza, they have not been tested for this purpose, dose or duration.”
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