Researcher Pursues Cure to Lung Disease That Steals Decades From Women’s Lives

In 2023, strange chest pains brought Aliza Gordon to an emergency room, where doctors discovered a partially collapsed lung and 20 tiny cysts, an oddity for a healthy, nonsmoking 37-year-old.

Two more lung collapses over the next six weeks forced Gordon, a New Jersey health care researcher with two young children, into surgery to affix her lung to her chest wall. After a biopsy, she received a terrifying diagnosis.

Gordon had lymphangioleiomyomatosis (LAM), a rare lung disease afflicting women—typically in their 30s, often after pregnancy—that progressively blocks oxygen flow. There is no cure, and life expectancy is 20 to 30 years after onset. Estimates vary, but some experts say the disease impacts 21 out of every million women. Some cases are genetic, others spontaneous, like Gordon’s.

“I was picturing my life in 10, 15 years—will I be able to walk on my own? Am I going to be carrying oxygen everywhere?” she recalled thinking. Her search for answers led her to the website of the Cincinnati-based LAM Foundation, a global health agency seeking a cure, where she saw a familiar face. 

Katharina Maisel, a University of Maryland associate professor of bioengineering and researcher in immunoengineering, had met Gordon 15 years prior, when she and Gordon’s now-husband worked together in a lab at Johns Hopkins University. Since then, Maisel has become one of the world’s few researchers advancing potential LAM treatments, recently publishing a breakthrough study in the American Journal of Respiratory Cell and Molecular Biology showing that mice with LAM live longer after inhaling a DNA strand found in the tuberculosis vaccine.

“This is a treatment that’s never been tried before, and in combination with current drugs and other immune treatments being developed, it could potentially lead to a cure,” said Maisel, whose study was funded by the American Lung Association. 

LAM cells lack a key protein regulator, causing them to multiply uncontrollably, like metastatic cancer. In healthy people, when the immune system detects abnormal cells going berserk, it kills them, but LAM and cancer cells alike have a “checkpoint inhibitor” that tricks the body into thinking they’re harmless. Resulting LAM cysts cause chest pain, shortness of breath and ultimately suffocation. 

The only drug found to stop progression, called rapamycin, can block the rapid cell division, but it’s not always effective and can prevent proliferation of healthy cells. 

Maisel learned about the disease as a University of Chicago postdoc studying lung lymphatics, a system of vessels that move fluid around the lungs to help clear congestion and prevent disease, among other functions. There, she met and began collaborating with LAM expert Vera Krymskaya, a professor with the University of Pennsylvania Perelman School of Medicine and the first to prove rapamycin’s effectiveness.

Maisel was curious about LAM’s cancer-like traits and its strange manifestation: The cells appeared to be ringed by lymphatic endothelial cells, suggesting that by treating one you could treat the other. There was another inspiration as well: Maisel had reached her late 20s, approaching the age of the disease’s average onset, and could easily empathize with women who would be blindsided by the diagnosis. “Think about a young mother who gets this diagnosis and is told, even with current drugs, you’ve got about 30 years,” she said. “It’s devastating.”

Krymskaya, now the LAM Foundation’s scientific director, called Maisel’s contributions important. “Katharina has developed a unique niche in LAM research, looking into immune responses, which can help with other therapeutic approaches,” she said.

In her study, Maisel used a mouse model of LAM, and had the rodent breathe in one of four molecules, each targeting a different immune receptor. One of them—CpG-ODN, which mimics bacterial DNA—jump-started the mice’s immune system, extending their lives from 45 to 60 days. When Maisel combined CpG-ODN with rapamycin, the mice lived for nearly 90 days.

Maisel’s next goal is to engineer a nanoparticle that can deliver CpG-ODN directly to the lymph nodes rather than the lungs, which are vulnerable to inflammation. She’s hopeful that collaboration with the small handful of LAM researchers worldwide can one day lead to human clinical trials. In the meantime, their collective research can advance treatments for common lung diseases like COPD, as well as cancer, Krymskaya said. 

After Gordon saw Maisel’s bio on the LAM Foundation website in 2023, she reconnected in an email. Maisel connected her with top LAM clinicians and a patient support community. 

Two and a half years later, Gordon has been symptom-free since recovering from surgery, save the occasional chest sensation, fortunate that she is not yet a candidate for medication, she said. She exercises more than ever and recently completed a pair of 5K races. 

She’s braced for symptoms to manifest someday, but in the meantime she’s traveling more and approaching life goals “with a bit more urgency,” she said. “I don’t know what the future will bring, but I’m hopeful.”