Every minute that went by put the patient more at risk. In his mid-30s, he was suffering from a massive heart attack with excessive blood clotting in the vessels around his heart. He had also tested positive for Covid-19.
Before beginning a procedure to clear the vessels and put in stents, Nathan and his team administered blood thinners, including Integrilin, to help break up the clots.
“Several hundred thousand heart attacks occur in the United States every year, and a significant proportion of these heart attacks are treated with agents, which unbeknownst to both the physician and patient, are actually derived from animal venom,” said Nathan, director of the University of Chicago Medicine’s Coronary Care Unit and co-director of its Cardiac Catheterization Lab.
“There’s a bit of a misconception that drug development, particularly with antiplatelets or anticoagulants, is now passé — that we’ve discovered everything that we need to know,” he added. “In my opinion, nothing could be further from the truth.”
Creating ‘designer toxins’
“We were approaching (venom-derived) compounds from two very different vantage points,” Nathan remembered Takacs telling him. “He wanted to discuss possibilities for academic collaboration and education.”
While Nathan administers the venom-derived drugs to his patients, Takacs is on the other end of the process — finding the original sources in the field: the venomous creatures themselves.
“What makes these creatures like a gold mine for medicine is actually the deadliness,” Takacs recently told CNN’s Dr. Sanjay Gupta. Toxins, he added, have been “tweaked by nature to take a life” with utmost efficiency.
“They aim (for) critical parts of the body, like the nervous function or the blood circulation. Those are the systems which you have to take under control in order to treat many different types of diseases.”
While the pandemic has slowed his usually hectic travel schedule — Takacs said he has visited more than 190 countries in his lifetime so far — his work continues through his partners in the field and in the lab.
“We’re actually not only creating toxin libraries, we’re doing a twist,” Takacs explained. “If we have a target for which there is not a good molecule which blocks that target, for example, then we look (to) nature. What kind of toxins around the world exist which target that particular molecule?”
In the lab, Takacs “chops up” the toxins into “bits and pieces” with genetic engineering, and rearranges the parts in every possible combination to create “mosaic toxins.” These variants still contain the “evolutionary wisdom,” he said, but differ slightly in biological activity.
“Then you screen this huge library to see which is the best match against the target of interest,” he said, in whatever disease you’re trying to treat.
From there, “it evolves into a drug lead and animal trials — and hopefully, in the long run, into clinical trials” with human participants.
Takacs said his latest research includes potential targets for Parkinson’s disease, cancer and gene therapy.
Looking to nature
References to venom as medical treatments also go back hundreds, if not thousands, of years. But it wasn’t until 1981 that the first FDA-approved, venom-derived medication hit the market, opening the door for a completely new class of medication, Takacs said.
“Toxins are good for so many different types of diseases, because there are so many of them in nature,” explained Takacs. “We have 150,000 venomous species combined. They have 20 million toxins, and 99.9% of the 20 million toxins in nature are unexplored.”
It’s that untapped potential that Takacs finds most promising, and that Nathan sees as critical for his cardiology patients, considering the current circumstances.
“I think the current pandemic that we’re in with Covid-19 and all of the coagulation-associated abnormalities has underscored the need for cleaner and more targeted anticoagulants,” Nathan said. “And this is only going to continue in the future.”