![\"A](\"https:\/\/www.freethink.com\/wp-content\/uploads\/2025\/07\/daniel-toker.jpg\")
That medical importance is what\u2019s driving Toker now. Perhaps his grandest aim is to cure coma and other disorders of consciousness, such as the vegetative state. Coma, a deep state of prolonged unconsciousness from which a person cannot be awakened, afflicts 258 out of every 100,000 Americans each year. Stroke, COVID-19, cardiac arrest, and a traumatic brain injury are common causes. Many of these people live in either a vegetative or minimally conscious state, in which they are fully \u201cawake\u201d but unaware, or only minimally aware, of their surroundings. As many as 300,000 Americans dwell in this gray area of consciousness. Those trapped in this haze are often referred to as \u201ccomatose.\u201d<\/p>\n\n\n\n
\u201cBecause vegetative patients are not really able to engage in the world, I think they\u2019re kind of hidden,\u201d Toker says. \u201cI could just be driving past some of these people\u2019s houses and I would never think that there\u2019s this patient there who\u2019s locked inside and basically tied to a bed and can\u2019t move. Because they\u2019re not visible. They can\u2019t go outside and walk. They can\u2019t advocate for themselves. You could be driving past them all the time, and you would have no idea.\u201d<\/p>\n\n\n\n
Disorders of consciousness can be devastating. They don\u2019t just consume the lives of those directly affected, Toker says.<\/p>\n\n\n\n
\u201cThey\u2019re cared for by their loved ones. They need to be on a feeding tube. They can\u2019t use the bathroom.\u201d<\/p>\n\n\n\n
Curing coma<\/h3>\n\n\n\n
So, how might medical research liberate those imprisoned by unconsciousness? Toker has several ideas.<\/p>\n\n\n\n
One that\u2019s in the very preliminary stages is modeling disorders of consciousness in brain organoids: small structures of brain cells grown in petri dishes from stem cells. If researchers can find a way to give them \u201ccomas\u201d (as signified by neuronal activity), perhaps via simulated brain injuries, they could test various compounds in an attempt to revert that activity to one emblematic of consciousness.<\/p>\n\n\n\n
Another route is through modeling coma \u201cin silico\u201d \u2014 in a computer. Toker recently led an effort<\/a> to train deep neural networks to detect consciousness across multiple brain areas, resulting in a realistic simulation of conscious brain states and disorders of consciousness. This will allow him and his colleagues to test whether varying types of deep brain stimulation can switch an unconscious simulated brain to a conscious state. They could then try these types of stimulation on comatose patients.<\/p>\n\n\n\n \u201cNow that we have a good model of a comatose brain, an awake brain, and an AI that can detect the difference, we can simulate stimulating every single brain structure at the whole-brain level.”<\/p>Daniel Toker<\/cite><\/blockquote><\/figure>\n\n\n\n Toker is perhaps most excited about a potential treatment derived from his own recently published research<\/a>. He trained an AI model on relevant data from the scientific literature to predict whether a drug can \u201cwake up\u201d someone based on its 3D structure.<\/p>\n\n\n\n \u201cThe AI was really good at it,\u201d he says. \u201cIt could pick up on bioactive structures in molecules that we might not even be thinking about or looking at.\u201d<\/p>\n\n\n\n But when the AI model finished its work and returned a list of potential pharmaceutical treatments, Toker was flummoxed. A diabetes medication stood far above all others.<\/p>\n\n\n\n \u201cI\u2019m sitting here on my laptop and the AI spits out its top predictions, and I\u2019m just like \u2018What\u2019s saxagliptin\u2019?\u201d he recalls.<\/p>\n\n\n\n Toker tweaked the algorithm’s parameters over and over, and it consistently returned the same answer: saxagliptin. Maybe the AI was onto something.<\/p>\n\n\n\n He found some preclinical work showing that the drug helps with Parkinson\u2019s and stroke. He then educated himself on how the drug functions. Saxagliptin inhibits DPP-4, an enzyme that breaks down GLP-1, a hormone now widely known because the new wave of weight loss drugs like Wegovy and Mounjaro mimic it to promote satiety. However, DPP-4 also alters the levels of a group of other brain-modulating compounds. <\/p>\n\n\n\n \u201cWhat became clear is that they seem to address all the known pathophysiologies of disorders of consciousness,\u201d Toker found.<\/p>\n\n\n\n So Toker had this promising result, but he still didn\u2019t know if it meant anything. He and his colleagues then cross-referenced it with something much more concrete. He checked UCLA\u2019s medical records of thousands of coma patients, and it became clear that people who were coincidentally on saxagliptin or other similar-acting drugs like Wegovy woke up from comas at significantly higher rates than coma patients who weren\u2019t.<\/p>\n\n\n\n Scientists know of other drugs that can boost arousal and awareness in comatose patients, but they are minimally effective. Amantadine<\/a>, an antiviral also used for Parkinson\u2019s, is most frequently used. The sedative Ambien<\/a> can also be weirdly effective. In rare instances, comatose patients regain awareness when the drug kicks in, but then lose awareness when it wears off.<\/p>\n\n\n\n Toker says that saxagliptin could be a new, more promising pharmaceutical tool. <\/p>\n\n\n\n \u201cWhat\u2019s tantalizing about this class of medication \u2014 it\u2019s acting through a completely different set of pathways that\u2019s different from anything else that we\u2019ve looked at for disorders of consciousness and coma.\u201d<\/p>\n\n\n\n Over video call, Toker was excited about the prospect of testing saxagliptin in a clinical trial on comatose patients.<\/p>\n\n\n\n \u201cPeople want their loved ones back. Especially in these chronic cases, it\u2019s so difficult, because they\u2019re there. They\u2019re alive. They\u2019re breathing. They\u2019re going to sleep. They\u2019re waking up. But they\u2019re not responding to anything.\u201d<\/p>\n\n\n\n But sharply tempering his excitement is the bleak state of funding for research into disorders of consciousness. <\/p>\n\n\n\n \u201cThis isn\u2019t something that pharmaceutical companies really care about,\u201d he says. Federal grants for this type of speculative research are also hard to come by, particularly for early-career scientists. And the cost of the ideal trial he envisions would easily exceed six figures. He would want at least 30 comatose patients to participate, so as not to miss a rare but meaningful effect: Someone might just regain awareness.<\/p>\n\n\n\n This article was reprinted with permission of\u00a0Big Think<\/a>, where it was\u00a0originally published<\/a><\/em>.<\/p>\n\n\n\nSaxa-what?<\/h3>\n\n\n\n
Trialing a promising treatment<\/h3>\n\n\n\n