From Sleeping Beauty to Buck Rogers to Austin Powers – suspended animation has long been a staple of fantasy and science fiction. The concept of suspended animation, beyond the magical spell that put Sleeping Beauty in her 100-year slumber, involves the slowing or stopping of biological functions without causing death.
Whether such technology will ever be developed that could enable humans to “hibernate” for long space voyages remains unknown, but we may be one step closer. The Defense Advanced Research Project Agency (DARPA), the research and development agency of the United States Department of Defense (DoD), is now partnering with Harvard University to explore how an FDA-approved drug to treat Alzheimer’s could be employed in “emergency situations” to create a type of brief suspended animation.
Past research has shown how certain drugs can slow numerous biological processes in animals to a crawl. It is believed that it could be used to buy additional time for a critically injured or ill patient. The catch is that the same compounds cause seizures in humans.
Researchers are now exploring how donepezil (DNP), which was developed to treat Alzheimer’s, could be used to place humans in a form of suspended animation. The drug has been used to put tadpoles of Xenopus laevis frogs into a hibernation-like state.
Cool It Down
The research is being supported as part of the DARPA Biostasis program, which “aims to extend the time for lifesaving medical treatment, often referred to as ‘the Golden Hour,’ following traumatic injury or acute infection, thus increasing survivability for military personnel operating in far-forward conditions with limited access to medical professionals or trauma centers.”
Biostasis has been investigated in how it could alter the time course of the pathological processes associated with tissue damage and infection by looking into how polymer chemistry, protein engineering, and deep cell activity monitoring can be employed by methods that aren’t dependent upon reducing temperature.
“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,” the study’s co-author Michael Super, director of immuno-materials at the Wyss Institute, told The Harvard Gazette. “Achieving a similar state of ‘biostasis’ with an easily administered drug like DNP could potentially save millions of lives every year.”
The Wyss Institute has been a partner in the Biostasis program since 2018.
AI Helping With its Development
While suspended animation remains a stable of science fiction, another sci-fi technology is helping with its development – namely artificial intelligence. The Wyss Institute has been utilizing predictive machine learning and AI algorithms with animal models to identify the drug compounds that could have the potential to put living tissues into a stage of suspended animation.
The efforts had previously identified the drug compound SNC80, which does have the potential to put living tissues into a “state of suspended animation,” the Harvard report noted. It was successful in significantly reducing oxygen consumption in both a beating pig heart and in human organ chips. The oxygen consumption served as a proxy for the metabolism. Yet, SNC80 is one of those drugs that can cause the aforementioned seizures.
The researchers employed their algorithm to identify other compounds that had a structure similar to SNC80, and the top candidate was DNP – a drug that was first approved to treat Alzheimer’s in 1996. It is used to treat symptoms of the disease including memory loss and confusion, and works by improving a user’s attention, memory, and even ability to engage in daily activities.
It is worth adding that donepezil isn’t a cure for Alzheimer’s or dementia.
More Than Side Effects of DNP
The study has also examined what may have been previously simply viewed as the side effects of DNP.
“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. 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,” said the study’s first author, María Plaza Oliver, a postdoctoral fellow at the Wyss Institute when the work was conducted.
It will still be a while before DNP – or other drugs – could allow for a true form of suspended animation, but this compound could have an advantage in that it can be more easily studied.
“Donepezil has been used worldwide by patients for decades, so its properties and manufacturing methods are well-established,” said senior author Donald Ingber, Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital.
“Lipid nanocarriers similar to the ones we used are also now approved for clinical use in other applications,” added Ingber, who is also a Hansjörg Wyss Professor of Bioinspired Engineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences. “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, and it could be easily formulated and produced at scale on a much shorter time scale than a new drug.”
The full findings of the study, “Donepezil Nanoemulsion Induces a Torpor-like State with Reduced Toxicity in Nonhibernating Xenopus laevis Tadpoles” were published in the August 21, 2024, edition of the journal ACS Nano.
