Old Treatments, New Life at the Sarver Heart Center
Sarver Heart Center Director and Allan C. Hudson & Helen Lovaas – Endowed Chair of Cardiovascular Medicine Hesham Sadek is exploring the ways FDA-approved therapies can be repurposed for novel uses — a prospect that could transform patient care.
The Sadek Lab at the Sarver Heart Center
The history of drug discovery is in part a history of happy accidents, of off-target effects that end up proving more useful to patients and durable in the marketplace than whatever the drug was originally designed for.
The hair-loss drug minoxidil, for example. Originally developed as an ulcer treatment in the 1950s, it was approved by the FDA in 1979 to treat hypertension after being found to lower blood pressure. The hypertension patients began to spontaneously — and rapidly — grow hair, hence the role the drug has today. Or Viagra, which was developed to treat angina; or, more recently, the exploration of ketamine — originally an anesthetic — as a possible treatment for depression.
Or the osteoporosis drug stumbled on by Sarver Heart Center Director Hesham Sadek. In 2017, while serving a joint appointment as a professor of cardiology and associate director of a center for regenerative medicine at the University of Texas Southwestern Medical Center in Dallas, Sadek got some unsettling news: His younger son had developed a genetic mutation in his heart. A rare diagnosis, Sadek says — something fewer than 300 people in the world shared. “‘There’s really no treatment for this disease,’” he remembers the doctor telling him. “‘We’re going to need a heart transplant.’”
At the time, much of Sadek’s work revolved around the question of whether the human heart had the capacity to regenerate. Medicine said no; science was open to possibility. In 2011, Sadek, who was trained as both a cardiologist and a biologist, had coauthored a paper called “Transient Regenerative Potential of the Neonatal Mouse Heart” in the journal Science that posited that the mammalian heart can regenerate for a brief period after birth. The paper changed both his own trajectory and — “and I’m not trying to sound too cocky,” he cautions — the trajectory of the field: Instead of trying to slow a process of inevitable and irreversible decline, the goal became to understand how treatment might reactivate the heart’s ability to heal itself.
When his son’s doctor came to him with the recommendation of a heart transplant, Sadek paused: Maybe a transplant wasn’t the only option. After crystallizing his son’s mutated protein and testing its response to various treatments (a process called a drug assay), Sadek found that not only did a drug that could correct the function of his son’s cells exist, it had already been approved by the FDA — for osteoporosis. It was a surprise, he says. “An absolute, complete surprise.”
Hesham Sadek, Sarver Heart Center Director and Allan C. Hudson & Helen Lovaas – Endowed Chair of Cardiovascular Medicine
Not everyone has as well-resourced and passionately invested a party to oversee their medical care, nor does Sadek expect drug companies to invest billions of dollars pursuing new treatments for conditions that affect 300 people. (“They’re publicly traded companies,” he says. “They need to make a profit.”) But Sadek thinks we’re closer to these sorts of individualized breakthroughs than we used to be, and envisions the Sarver Heart Center as a place where patients facing rare cardiac conditions might come and have a little hope, potentially in the form of a known drug whose full range of effects has yet to be discovered.
Sadek cites how advances in software — including the artificial intelligence program AlphaFold, whose co-inventors won the Nobel Prize for chemistry in 2024 — have streamlined the process by which protein structures can be modeled and, in turn, matched with potential treatments that can meaningfully interact with them. “Instead of me finding a protein that I think would be important for the disease and then spending the next four or five years trying to crystallize it and another three or four years trying to find a drug that would attach to the crystal structure that I found,” he says, “I can log on to AlphaFold, and within two hours I’ll have the actual structure of the protein.” Years become hours, and drugs once seen as points of conclusion instead become points of potential.
Part of what brought Sadek to the Sarver Heart Center in 2024 was the prospect of being able to marshal talented people from different disciplines and perspectives together toward the achievement of a common goal — or at least to get them to better understand where their peers are coming from. “I want a physicist who is developing a new microscope next to a biologist who’s studying contractile protein next to a computational mathematician who’s developing a software for modeling of a heart cell contracting, right?” he says. (Right.)
“When you’re hyperspecialized, you don’t really see outside your field. You might have a tool that can solve a problem, but you don’t know who has that problem. And I think bringing those people together under one roof is enough sometimes.”
Sadek’s vision is in some ways an outgrowth of his training. “Many big discoveries were made by physician-scientists or doctors who saw a problem in the clinic and tried to solve it in the lab,” he says. “My goal is to make the Sarver Heart Center the first in the nation, probably in the world, that will open up to patients with rare cardiovascular disease — but also any rare disease: Identify the cause of the problem, take it to the lab, study it in their own cells and culture, come up with a screen using FDA-approved drugs and take them back to patients.” The decision trees of the physician and the exploration of the scientist; the black-and-whiteness of medicine with the gray of research.
Sadek acknowledges that he has an uphill battle. “That phenotype — my phenotype, the physician-scientist — is under threat,” he says. He remembers watching cardiologists he helped train at Southwestern walk away from research for ever-higher-paying jobs in private practice. They were married, the breadwinner, a new parent; faced with the choice of starting at $50,000 for the long haul of working in a lab versus 10 times as much immediately entering private practice — well. “There’s no comeback,” Sadek says. “It doesn’t matter how much you love it or how dedicated you are to the cause.”
Still, he has hope that with the right kind of support, he can turn Sarver into a place where talent can be nurtured and retained and generally saved from the temptations of what he calls “the dark side.” “We probably aren’t going to make a lot of money repurposing these drugs,” he says. “But we might treat even one patient, which would be our goal” — maybe someone’s son.