Scientists at the University of Queensland may have found a way to reverse the brain’s premature aging caused by COVID-19. The team led by Dr. Julio Aguado used brain organoids — miniature, lab-grown models of the brain grown from human stem cells — to untangle the mechanism through which the virus affects brain tissue. Armed with this knowledge, they then tested a range of substances and found not one but rather four drugs that could potentially reverse the damage.
The Battle Against ‘Zombie’ Cells
During their investigation, the Australian scientists discovered that the virus hastens the accumulation of ‘zombie‘ or senescent cells, which are typically associated with natural aging. Senescent cells turn undead with aging and stress — undead in the sense that they cease to replicate but also resist the immune system activity that flushes out dead cells.
“Senescent cells are known to drive tissue inflammation and degeneration, leaving patients exposed to cognitive impairments like brain fog and memory loss,” says Aguado.
We all know that symptoms of COVID-19 can vary widely. Some people shake it off easily, while others can get so sick they have to be intubated and some die. But another subgroup of patients showcases one of the coronavirus’s most insidious symptoms. Months after infection, some patients can’t shake the feeling that their brain is lost in a maze, and they can’t find their way back. This “brain fog” is a common complaint among patients with “long COVID”.
When the researchers analyzed brain tissue from deceased patients who had succumbed to severe coronavirus infections, they found at least seven times more proteins associated with zombie cells. It is likely that the infection with SARS-CoV-2 (the virus that causes COVID-19) triggered the cellular senescence.
This alarming finding prompted the team to seek a way to ‘turn back the clock‘ on these cells. Their quest led to the identification of four drugs that effectively cleared away these harmful cells: navitoclax, ABT-737, fisetin, and a dasatinib-quercetin combo (D+Q). These drugs showed promise both in rejuvenating the brain organoids and when used in a COVID-19-infected mouse model.
“Long term, we can expect widespread use of these drugs to treat persistent post-acute infection syndromes caused by viral infections like COVID-19,” said Aguado.
Such research highlights the power of brain organoids, which open doors for experiments that are typically difficult or unethical in humans. The same method could also revolutionize Alzheimer’s research and the treatment of various diseases where cell senescence is a factor.
“Our study beautifully demonstrates how human brain models can accelerate the pre-clinical screening of therapeutics — while also moving towards animal-free testing — with potentially global impacts,” said Professor Ernst Wolvetang, an organoid expert at the Australian Institute for Bioengineering and Nanotechnology.
The findings appeared in the journal Nature Aging.
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