The Defense Advanced Research Project Agency (DARPA) has partnered with Harvard University to explore putting humans into a form of suspended animation in life-threatening situations. Previous research has identified a drug that can slow numerous biological processes of animals to a virtual crawl, dramatically extending the time a critically injured or ill patient can survive. Unfortunately, that compound causes seizures in humans, limiting its potential use.
Researchers are now exploring a new approach that uses an already approved Alzheimer’s drug called donepezil (DNP) to potentially place humans in suspended animation. If approved, the rapid application of DNP in emergencies could offer first responders a potentially life-saving tool or even help future space travelers endure prolonged missions in “hypersleep.”
“Cooling a patient’s body down to slow its metabolic processes has long been used in medical settings to reduce injuries and long-term problems from severe conditions, but it can only currently be done in a well-resourced hospital,” said co-author Michael Super, Ph.D., Director of Immuno-Materials at Harvard University’s Wyss Institute. “Achieving a similar state of ‘biostasis’ with an easily administered drug like DNP could potentially save millions of lives every year.”
Suspended Animation Drug Could Extend the Critical “Golden Hour”
In the press release announcing the program, which is part of DARPA’s Biostasis initiative, the Harvard researchers note that finding a simple treatment to extend the critical “golden hour” after a patient suffers a critical injury or illness has long been a goal of health providers. As noted, some success has come from dramatically lowering a person’s body temperature. However, the researchers say this treatment is limited to a handful of medical facilities.
Instead, the Wyss Institute team looked for a simple-to-administrate drug therapy to achieve similar results. Previous to this effort, they had used a combination of computerized animal models and a predictive machine-learning tool called NeMoCad to explore potential drug options for placing an animal into suspended animation.
That effort identified a chemical compound known as SNC80, which “significantly reduced oxygen consumption (a proxy for metabolism) in both a beating pig heart and in human organ chips.” Unfortunately, SNC80 is unapproved for human use, as it is known to cause seizures when injected systematically.
Undaunted, the researchers went back to their simulation software, hoping to find drugs with similar enough chemical signatures and properties to achieve a similar suspended animation effect without the potentially deadly side effects of SNC80. Almost immediately, the team zeroed in on DNP. Along with a promising chemical signature, the researchers found that DNP had already offered real-world hints that it could slow the body’s overall metabolism in high enough doses.
“Interestingly, clinical overdoses of DNP in patients suffering from Alzheimer’s disease have been associated with drowsiness and a reduced heart rate – symptoms that are torpor-like,” explained Maria Plaza Oliver, Ph.D., who is the study’s first author and a Postdoctoral Fellow at the Wyss Institute when the work was conducted. “However, this is the first study, to our knowledge, that focuses on leveraging those effects as the main clinical response and not as side effects.”
DNP Could See Fast Approval Due to its Currently Approved Status
In their study, the team points out that this is only a first step toward finding an actual suspended animation treatment. However, they also note that DNP’s status as an already approved drug that is easy to manufacture and distribute could make the process of approving it for this type of function dramatically shorter than that of a new chemical compound.
“Donepezil has been used worldwide by patients for decades, so its properties and manufacturing methods are well-established,” said senior author Donald Ingber, M.D., Ph.D. Ingber is the Founding Director of the Wyss Institute, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences. “Lipid nanocarriers similar to the ones we used are also now approved for clinical use in other applications.”
“This study demonstrates 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,” Ingber added, “and it could be easily formulated and produced at scale on a much shorter time scale than a new drug,”
Although not a part of the team’s study, the drug could theoretically offer a potential solution for future space travelers who must endure extended flight times with limited resources. While this method of “hypersleep” is commonplace in science fiction, the discovery of a simple drug compound that can achieve a similar effect is a significant step toward making this possibility a reality.
“Donepezil Nanoemulsion Induces a Torpor-like State with Reduced Toxicity in Nonhibernating Xenopus laevis Tadpoles” appears in the August 21, 2024, edition of the journal ACS Nano.
Christopher Plain is a Science Fiction and Fantasy novelist and Head Science Writer at The Debrief. Follow and connect with him on X, learn about his books at plainfiction.com, or email him directly at christopher@thedebrief.org.