Tag Archives: alpha

New trial will try to stop the “cytokine storms” that make COVID-19 cases deadly

Our own immune systems may be to blame for producing some of the worst symptoms of COVID-19, through a process known as a “cytokine storm”. Now, new research plans to fix this.

image credits Engin Akyurt.

The prolonged, high fevers, severe respiratory distress, and lung damage seen in some critically ill patients are actually caused by our immune systems trying (way too hard) to fight off the infection, not by the virus itself. New research at the Johns Hopkins University School of Medicine plans to test the efficiency of a prescription drug called an alpha-blocker as a protection against this process.

A cure for storms

“The approach we’re advocating involves treating people who are at high risk early in the course of the disease, when you know they’re infected but before they have severe symptoms,” says Bert Vogelstein, chief investigator on this project.

The team is setting up a clinical trial with patients ages 45 to 85 who have COVID-19 but who aren’t on a ventilator or in the ICU. These participants will help establish whether alpha blocker prazosin can be used to stop macrophage activation syndrome, or “cytokine storms“, by preventing hyper-inflammation in response to the infection.

Such an effect has been documented in mouse studies, the team explains. If alpha blockers are found efficient in humans as well, they could help keep more people safe at home where they can recover without taking up hospital resources, which are already spread thin.

Exaggerated immune responses aren’t unique to COVID-19, as people with autoimmune diseases and cancer patients receiving immunotherapy can attest.

Cytokines are chemical messengers used by our immune systems to organize against a threat. In moderation, they help immune cells converge to where they’re needed and fight off the infection. However, our bodies also use signaling molecules called catecholamines when a more heavy-handed response is needed, and they trigger the release of more cytokines — this process can form a feedback loop that drives our immune cells berserk.

“It seems that once this process starts, there’s this inability to properly switch it off,” says Maximilian Konig, a rheumatologist at Hopkins who is helping to coordinate the trial.

Alpha blockers interfere with the signaling pathways of cytokines, and Vogelstein’s past research on mice has found that they can be used to lessen cytokine storms and decrease mortality rate without having adverse effects on our immune response.

Giving mice with bacterial infections an alpha-blocker lessened cytokine storms and decreased deaths, Vogelstein’s team reported in the journal Nature in 2018. And, the researchers found, the treatment didn’t seem to harm other aspects of the immune response.

The patients in this trial will be given gradually-increasing doses of prazosin over six days, and will then be monitored to see if they have a lower ICU admission rate or ventilator use than patients who received the standard treatment. The trials will last for 60 days but preliminary data could be available within a few weeks, according to the team.

The paper “Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists” has been published in the Journal of Clinical Investigation.

Honeybee brains could be a good model to study human brains on

New research from the University of Otago and the University of Heidelberg found that bee and human brains have some surprising similarities.

A bumblebee looking epic.
Image credits Harry Strauss.

Both human and honey bee brains generate alpha oscillations (the cyclic patterns of electrical activity neurons generate, also known as ‘waves’) with surprisingly similar properties, the study reports. The findings could help us better understand brain functions such as attention, memory, and consciousness, and point to a novel way of studying the human brain.

Bee-brained

“Experiments on humans are expensive, logistically difficult, and time consuming. Moreover, recordings from individual identified neurons are not possible in human brains. By studying the brains of bees we can overcome these limitations and apply that knowledge to research, and eventually perhaps even to treatment, of human brains,” explains Paul Szyszka, Lecturer in the University of Otago’s Department of Zoology and the paper’s second author.

Szyszka collaborated with Dr. Tzvetan Popov of the University of Heidelberg in Germany, the study’s lead author, to study the brains of regular honey bees living in outdoor hives. The duo took bees into the lab, implanted microscopic electrodes into their brains to record patterns of neural activity, and then set about stimulating them with various odors. The team would also feed these bees a sucrose solution (i.e. sugar water) from a pipette while they were exposed to certain odors.

In the end, the duo found that bees can learn to associate odors with food in a similar way to humans and other primates. They further found that the process elicited similar changes in alpha waves in the bees’ brains as have been observed under similar conditions in humans and other primates. As such, they say the findings “suggest a common role of alpha oscillations across phyla and provide an unprecedented new venue for causal studies on the relationship between neuronal spikes, brain oscillations, and cognition.”

“What we want to do now is examine how these alpha oscillations change in different situations. As a neuroethologist, I’m interested in how bees’ alpha oscillations change during natural behaviors, for example when a bee forages or sleeps,” Szyszka says.

Szyszka is now looking for Zoology or Neuroscience master students to collaborate with on continuing this research. He is particularly interested in studying the relationship between brain waves, learning, and memory.

The paper “Alpha oscillations govern interhemispheric spike timing coordination in the honey bee brain” has been published in the journal Proceedings of the Royal Society B.