Source:
FEBRUARY 21, 2024 6:23 AM EST
Geneticist Marlena Fejzo had a difficult start to her first pregnancy. She suffered from nausea and vomiting, as roughly 70% of pregnant people do, but pushed through until the symptoms lessened with time.
Her second pregnancy, in 1999, was another story. For weeks, all Fejzo could do was lie flat on her back, since even rolling to her side triggered debilitating nausea. Eating or drinking was out of the question, forcing her to get a home IV for nourishment. “Every second,” she says, “was torture.”
Fejzo, who is now 56 and a clinical assistant professor at the University of Southern California’s Keck School of Medicine, had something more serious than typical morning sickness. She was ultimately diagnosed with hyperemesis gravidarum (HG), a condition that leads to extreme nausea and vomiting in 1% to 3% of pregnancies.
But even as her doctor diagnosed her, he downplayed the situation, suggesting that many women with HG exaggerate their symptoms for sympathy. Fejzo knew he was wrong; the idea of making up such misery was ludicrous. But she “didn’t have the energy to fight.” By that point, she was bedbound and losing weight at an alarming rate.
Fejzo’s physician eventually ordered a feeding tube, at around 11 weeks of pregnancy, but it wasn’t enough. Fejzo had become so frail that she lost her fetus just a few weeks later. “It was just too late,” she says.
Haunted by her doctor’s dismissal and the limits of his care, Fejzo tried to learn whatever she could about HG while she recovered. That turned out to be not much at all—the condition was barely studied at the time. (Many would only learn about HG when British royal Kate Middleton was hospitalized with it during her pregnancies.) “There was so little known,” Fejzo says, but she had a hunch “there was something biological going on.” She vowed to be the one to find out what it was, both for her own sake and that of her future children, twin daughters who were later born via surrogate. “I didn’t want my daughters to have to go through that,” she says. “Or anybody else.”
Fejzo was uniquely well suited to the task. She’d been interested in women’s health since her Ph.D. training in genetics at Harvard University, when she discovered two genes linked to developing potentially painful uterine growths known as fibroids. She’d gone on to research breast cancer at the University of California, San Francisco, and multiple sclerosis at the University of California, Los Angeles. Motivated by her “horrible experience” and the memory of being blamed for it, she turned her scientific expertise toward her own condition.
She began by setting up an online survey to learn more about the experiences of other people who’d had HG, the results of which suggested the condition ran in families—many sufferers said their mothers or sisters had also lived through it. Even more painstakingly, Fejzo spent a decade calling people who had suffered through HG, one by one, to ask for saliva samples she could use in genetic studies down the line. She collected plenty of samples, but at first struggled to persuade funders to pay for costly genetic research.
Then, in 2010, she took a 23andMe DNA test that changed everything. When Fejzo saw the survey 23andMe sends to its customers to learn more about how their genes relate to their health, it sparked an idea. She persuaded the company to include questions about HG in its survey, and by 2016 she had access to genetic data and survey responses from about 50,000 people.
By analyzing that trove of data, Fejzo was able to zero in on two genes of interest. One, in particular, seemed promising: it codes for the hormone GDF15, which is linked to appetite suppression and vomiting—and which the body produces in earnest during pregnancy. In 2018, she published a paper in Nature Communications suggesting that a variant of that gene could predispose people to HG. She later bolstered that finding, discovering a rare genetic mutation that seemed to be even more strongly linked to developing HG.
Spurred by those discoveries, Fejzo quit her position in a UCLA cancer laboratory in 2020 to focus on researching HG. It wasn’t difficult to leave, she says. “There’s tons of people working on cancer, and I’m one of the only people working on hyperemesis. If I stopped working on it, the road would have ended.” She wasn’t willing to let that happen.
Last year, more than two decades after her harrowing experience with HG, Fejzo had another breakthrough. In a paper published in Nature, she reported that people with HG tend to have high blood levels of GDF15 during pregnancy, yet produce lower-than-average amounts of GDF15 prior to pregnancy. When GDF15 levels naturally rise after conception, the shock to the system results in HG’s relentless nausea and vomiting.
That finding opens up promising avenues for treatment. Doctors could lower GDF15 levels during pregnancy. Or, if they could gradually supplement levels of the hormone in people who are not yet pregnant but deemed high-risk based on personal or family history of HG, they could feasibly smooth the transition and avoid debilitating symptoms. Fejzo is now applying for funding for a clinical trial to test whether the drug metformin—which is approved to treat Type 2 diabetes but is used off-label for numerous purposes and has been shown to raise GDF15 levels—works as a preventive therapy.
It may take years to find out whether that approach works, but if it does, Fejzo will be able to act quickly. In addition to serving on the board of the Hyperemesis Education & Research Foundation, Fejzo is the chief scientific officer at a new women’s health company, Harmonia Healthcare, which this year plans to open an HG-focused treatment center in New Jersey before expanding to New York City. “I’ve been trying for so long to put an end to this,” Fejzo says, “and I think we’re finally close.”
WRITE TO JAMIE DUCHARME AT JAMIE.DUCHARME@TIME.COM.
Comments