The Defense Advanced Research Project Agency (DARPA) has partnered with Harvard University to study how to put people in a state of suspension in life-threatening situations. Previous research has identified a drug that can slow numerous biological processes in animals to a virtual crawl, dramatically increasing the survival time of a seriously injured or ill patient. Unfortunately, this compound causes seizures in humans, limiting its potential use.
Researchers are currently studying a new approach that uses an already approved Alzheimer’s drug called donepezil (DNP) to potentially put people into a state of suspended animation. If approved, the rapid use of DNP in emergency situations could provide first responders with a potentially life-saving tool or even help future space travelers survive longer missions in “hyper sleep.”
“Cooling a patient’s body to slow down its metabolic processes has long been used in medicine to reduce injury and long-term problems in severe disease, but currently it is only possible in well-equipped hospitals,” said co-author Michael Super, Ph.D., director of immune materials at Harvard University’s Wyss Institute. “Achieving a similar state of ‘biostasis’ with an easily administered drug such as DNP could potentially save millions of lives each year.”
Drug against apparent death could extend the critical “golden hour”
In the press release announcing the program, part of DARPA’s Biostasis Initiative, the Harvard researchers point out that finding a simple treatment to extend the critical “golden hour” after a patient has suffered a serious injury or illness has long been a goal of healthcare providers. As mentioned, some success has been achieved by 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 an easy-to-administer drug therapy that would produce similar results. They had previously used a combination of computational animal models and a predictive machine learning tool called NeMoCad to explore potential drug options for putting an animal into a state of suspended animation.
They identified a chemical compound called SNC80 that “significantly reduced oxygen consumption (an indicator of metabolism) in both a beating pig heart and human organ chips.” Unfortunately, SNC80 is not approved for use in humans because it is known to cause seizures when systematically injected.
Undaunted, the researchers turned again to their simulation software, hoping to find drugs with sufficiently similar chemical signatures and properties to produce a similar effect of suspended animation without SNC80’s potentially fatal side effects. Almost immediately, the team focused on DNP. In addition to a promising chemical signature, the researchers found that DNP had already shown real-world evidence that, in high enough doses, it could slow the body’s overall metabolism.
“Interestingly, clinical overdoses of DNP in patients with Alzheimer’s disease have been associated with drowsiness and reduced heart rate – symptoms reminiscent of freezing,” explained Dr. Maria Plaza Oliver, the study’s first author and a postdoctoral fellow at the Wyss Institute at the time the work was conducted. “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.”
DNP could receive rapid approval due to its current approval status
In their study, the team points out that this is only a first step toward an actual treatment for suspended animation. However, they also point out that DNP’s status as an already approved carpet that is easy to manufacture and distribute could make the approval process for this type of function much shorter than that of a new chemical compound.
“Donepezil has been used by patients around the world for decades, so its properties and manufacturing processes are well established,” said senior author Donald Ingber, MD, Ph.D. Ingber is founding director of the Wyss Institute, Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and 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 now approved for clinical use in other applications as well.”
“This study shows that an encapsulated version of the drug could potentially be used in the future to buy patients the critical time they need to survive devastating injuries and diseases,” Ingber added. “And it could be easily formulated and produced on a large scale and in a much shorter timeframe than a new drug.”
Although the drug was not part of the team’s study, it could theoretically offer a potential solution for future space travelers who must endure long periods of flight with limited resources. While this method of “hypersleep” is commonplace in science fiction, the discovery of a simple drug compound that can produce a similar effect is an important step toward making this possibility a reality.
“Donepezil nanoemulsion induces a torpor-like state with reduced toxicity in non-hibernating Xenopus laevis tadpoles“ will appear in the August 21, 2024 issue of the journal ACS Nano.
Christopher Plain is a science fiction and fantasy author and senior science writer at The Debrief. Follow and contact him on X, Find out about his books at plainfiction.com or email him directly at [email protected].
