The next great stroke treatment might borrow a bit from science fiction. Research out today shows that keeping someone on ice might help protect their brain from stroke-related injury.
Scientists at the Beijing Institute for Brain Disorders in China and others used a two-drug combination to clinically induce hypothermia in both lab animals and people. In animals, lowering body temperature appeared to slow metabolism and delay the development of brain damage from a stroke, while the treatment seemed to be safe and well tolerated in an early trial involving stroke patients. The researchers are now calling for larger trials of induced hypothermia—a kind of survival mode—to treat stroke and other similar conditions.
“Hypothermia and hypometabolism hold promise for helping patients with acute severe disease,” the researchers wrote in their paper, published in Science Translational Medicine.
Freezing a stroke
As dangerous as hypothermia can be, scientists have long wondered whether it could be used to help treat a variety of medical problems. Lowering body temperature can also slow cellular metabolism, which may in turn prevent or at least limit the destructive processes that some cells undergo during certain medical conditions like stroke.
Induced hypothermia is actually already used sometimes following cardiac arrest (the sudden loss of a heartbeat due to an electrical malfunction) to limit brain damage. Right now, though, it’s only used on unconscious patients, largely because a conscious body will try to actively resist this cooling, such as by heavily shivering. Awake people also typically can’t tolerate physical methods of hypothermia for very long and can experience serious bodily stress, making the treatment riskier.
According to the researchers, studies have shown that certain drugs and other interventions like ultrasound can induce hypothermia in mice without literally needing freezing temperatures. But it’s an open question as to whether these methods can safely do the same in large primates like humans, much less whether this hypothermia can then help treat stroke.
For their experiments, the researchers turned to a combination of chlorpromazine, a first-generation antipsychotic, and promethazine, a long-used histamine.
They first tested the drugs on mice and rhesus macaques with stroke. In both animals, the treatment seemed to protect their brains and reduce the risk of neurological complications. The researchers then deployed the drugs in a phase I, placebo-controlled trial of 32 patients with acute ischemic stroke (the most common type of stroke, caused by a blood vessel blockage in the brain). The patients were either given a placebo or one of four varying doses of the drug combination.
Phase I trials are primarily intended to test a treatment’s safety, and all four dosages appeared to be safe and well-tolerated in the patients. The researchers also detected biomarkers of reduced metabolism in all of the treatment groups, though only the highest dose seemed to reliably lower people’s body temperature.
What comes next
Animal experiments and early human trials are only the beginning of proving that an experimental treatment can work as hoped, obviously. But these results are enough to keep pushing ahead, the researchers argue.
“Evidence spanning rodents, rhesus monkeys, and patients with stroke demonstrates the translational potential of C+P treatment,” they wrote. “This study may serve as a basis for further phase 2 studies.”
And should the team’s research continue to pay off, they’re hopeful that induced hypothermia will emerge not only as a treatment for stroke but also for other critical emergency situations, such as severe bodily trauma or sepsis.
With any luck, freezing a stroke might someday become the standard of care.
