Why HIBERNATION could save stroke victims’ lives

Hibernation sounds so tempting on icy, dark mornings — burrowing under the duvet to snooze until spring.

now, scientists are racing to make human hibernation a reality — not to escape winter, but, for example, to help provide precious time for cancer treatment to work. and that’s not all.

as Mervyn Singer, a professor of intensive care and medicine at University College London Hospital, reveals exclusively in Good Health, his team is trialling a drug that may soon be used to make vital human tissues such as hearts, brains and arteries go into a hibernatory ‘sleep’ mode.

this could potentially save the lives of thousands of heart attack and stroke patients every year.

Professor Singer believes it could protect these cells against lethal trauma that can occur during emergency resuscitation procedures. the trauma — called ‘reperfusion injury’ — occurs when blood flow is suddenly restored to tissue that has had its supply blocked, such as heart and artery cells in heart attack and brain cells in stroke.

it seems common sense to restart heart attack and stroke patients’ circulations as soon as possible — for example, by inserting a wire-mesh tube (stent) to prop open blocked arteries.

but the shock of a sudden return of blood and oxygen can spark an inflammatory reaction that destroys vital artery, heart and brain tissues in up to a third of patients, and can prove lethal.

if Professor Singer’s first human trial, scheduled for next year, shows the drug can protect patients from reperfusion injury, it would provide the first workable hibernation treatment breakthrough in 20 years of global efforts.

SCientiStS

have spent decades studying hibernating animals and their ability to slow their pulses and drop their body temperatures to the point of near-death for months on end — without damaging their brains and vital organs.

the hope is that such biological feats can be copied and used to create drug therapies for diseases including diabetes, alzheimer’s and cancer.

Last month, researchers revealed that their studies show a biological trick performed by hibernating squirrels could prove key to developing a drug to protect stroke patients from brain damage.

Scientists from the U.S. national institute of neurological Disorders and Stroke say that when squirrels hibernate, a protective process occurs in their cells that allows their brains to survive the reduced blood flow cutting vital supplies of oxygen and glucose.

the process, called SUMoylation, changes the way that proteins behave in the torpid squirrels’ brain cells, protecting them from damage. the neuroscientists say they have found a chemical in the brain, called SenP2, that stops SUMoylation happening in wide-awake squirrels.

they discovered that by blocking the brain chemical in mice, SUMoylation takes place. Scientists hope to develop a drug that sparks a similar response in human brains.

‘if we could turn on the process hibernators use, we could help protect the brain during a stroke,’ says Joshua bernstock, the neuroscientist who led the study.

Meanwhile, italian scientists are exploring the possibility of putting cancer patients into a hibernation state in which their whole bodies could be cooled from a norm of 37c to a deathly chilled 13c.

Professor Marco Durante, a physicist at the trento institute for Fundamental Physics applications, hopes this will bring bodily functions to a virtual standstill and give doctors more time to try to kill off tumours with radiation.

it is not yet technically possible to hibernate a human body in a way that could safeguard brains and vital organs from severe damage, but Professor Durante believes this will be achieved within the next decade.

in February, at a conference for the american association for the advancement of Science, he said: ‘i’m confident we will be able to develop drugs that can induce this torpor safely.’

His optimism is not shared, however, by Vladyslav Vyazovskiy, an associate professor of neuroscience at the University of oxford. He is part of a team organised by the european Space agency to discover how to put humans into hibernation so they could survive missions to Mars, a feat he believes could be decades away.

‘the key issue is that we do not yet have a good understanding of how hibernation is generated and regulated in animals,’ he says. Hibernating animals have developed the ability to let their brains’ internal communications links — their ‘synaptic networks’ — fall apart during their winter sleep. but as the animals wake, the networks restore to full function.

‘We need to do more work to understand this process better before we can safely and efficiently put a human being in torpor,’ warns Professor Vyazovskiy.

these are massive challenges — but they could have huge benefits. in patients with alzheimer’s disease, the brain’s synaptic connections fall apart, causing confusion and memory loss.

if investigators could learn the hibernators’ trick of rebuilding those connections, ‘ there is a possibility therapeutic hibernation could be used for preventing or treating alzheimer’s disease’, says Professor Vyazovskiy.

Meanwhile, Professor Singer is forging ahead with a world-first hibernatory drug trial for heart attack and stroke patients — by putting a targeted part of their body or brain into hibernation.

‘if you have a heart attack, some of the tissue dies, but the surrounding cells shut down to protect themselves from the loss of blood supply,’ he explains.

‘this “myocardial hibernation” has been known about for 20 years. a similar process happens in the kidneys after kidney failure, and in the brain after a stroke.

‘the cells shut down in the hope the physical problem will repair itself, the organ’s function will return and the hibernating cells can re-awaken and recover.’

back in 2005, a research team in Seattle discovered that if you give hydrogen sulphide gas to a mouse, its heart rate and temperature drops and it will go into hibernation within about an hour. once the gas was stopped, the mouse returned to normal.

However, hydrogen sulphide has proved poisonous in the doses that are required to induce hibernation in humans.

it is the sulphide molecules in the gas that prompt the hibernation response, so Professor Singer’s team is working to perfect a drug that safely delivers the sulphide.

the best way to do that is to induce hibernation in cells only in specific areas.

this promises to have great benefit in stopping a common complication of the emergency treatment given to heart attack and stroke victims, where if an organ’s blood supply is disrupted, ‘you can cause further damage by rapidly restoring the blood supply’, says Professor Singer.

THiS

is a common and potentially lethal problem in emergency treatment. ‘ the sudden flood of returning blood causes the cells to release a torrent of free radicals, chemicals, which, in turn, can cause inflammation, leading to further catastrophic organ damage,’ says Professor Singer.

but putting these cells into hibernation for just a few minutes while the blood supply is rapidly restored (or reperfused) means the cells can’t react. Professor Singer has been using a drug that acts like hydrogen sulphide, which can be used in localised parts of the body, such as the coronary artery in heart attack patients.

‘We have been doing this in animal models and have been able to reduce the reperfusion damage by up to 50 per cent,’ he says.

‘Hopefully, we will be able to advance into human trials by the end of next year.’