Drug against “suspended animation” could buy time in medical emergencies

In a medical emergency, prompt treatment is critical, but a widely used drug could be repurposed to induce a sleep-like state, slow organ damage and save lives by giving patients more time to reach a hospital.

Doctors often speak of the “golden hour” as the crucial time immediately after a traumatic injury. Although it is not exactly an hour, the general principle is that the faster a medical intervention is carried out, the better the patient’s chances of survival.

This is obviously a big problem in emergencies that take place far from a hospital. But a new study from Harvard's Wyss Institute proposes a new way to extend this so-called golden hour by putting a patient into “biostasis” to slow their metabolism and prevent permanent organ damage.

The researchers used an algorithm called NeMoCad, which analyzes the structures of compounds to figure out which ones might have a desired effect—in this case, inducing torpor, a type of hibernation that some animals naturally enter. This process crystallized a compound called donepezil, or DNP, which is currently FDA-approved as a treatment for Alzheimer's disease.

“Interestingly, clinical overdoses of DNP in patients with Alzheimer's disease have been associated with drowsiness and reduced heart rate – symptoms reminiscent of freezing,” said María Plaza Oliver, lead author of the study. “However, to our knowledge, this is the first study to focus on using these effects as the main clinical response rather than as side effects.”

The team tested the possible sleep-inducing effect of DNP in tadpoles. And indeed, it reduced three biological factors that indicate a sleep-inducing effect: oxygen consumption, heart rate and swimming motion.

Unfortunately, when injected as free particles, the drug accumulated in the tadpoles' tissues and caused some toxicity. To prevent this, the team encapsulated the DNP in lipid nanoparticles and found that the drug accumulated in brain tissue, reducing toxicity while still inducing the torpor-like state.

The results are fascinating, but of course tadpoles are still a long way from humans. More testing will be needed to determine exactly how it induces torpor, but on the plus side, this testing route should be easier than for many drugs. DNP has been used clinically in humans for nearly 30 years.

“Donepezil has been used by patients around the world for decades, so its properties and manufacturing processes are well established,” said Donald Ingber, senior author of the study. “Lipid nanocarriers similar to the ones we used are now also approved for clinical use in other applications. This study shows that an encapsulated version of the drug could potentially be used in the future to buy patients critical time to survive devastating injuries and diseases, and it could be easily formulated and produced at scale in a much shorter timeframe than a new drug.”

Other studies have found that ultrasound pulses aimed at specific areas of the brain can induce a state of torpor, which is also thought to save lives during surgery and, in the more distant future, may help astronauts enter a state of “hypersleep” during long space journeys.

The study was published in the journal ACS Nano.

Source: Wyss Institute