Scientists from the University of Cincinnati have potentially uncovered a treatment for lymphangioleiomyomatosis (LAM), a rare pulmonary disease primarily affecting women in their reproductive years. By focusing on a newly identified dysfunctional biological pathway, two already approved drugs may serve as effective treatments, and perhaps even a cure, for LAM.
The findings hold promise for curing LAM, a condition for which the exact etiology is still unknown and no definitive cure has been established. The research, backed by the National Heart, Lung, and Blood Institute, has revealed that two existing pharmaceuticals may offer promise in mitigating the effects of LAM, thereby opening a path toward a possible cure.
The research was recently documented in the scholarly journal Science Advances.
“The precise number of women affected by LAM remains uncertain; however, estimates suggest that between three and seven women per million globally are afflicted,” states Tasnim Olatoke, a third-year graduate student at the UC College of Medicine and the study’s lead author. “LAM is a life-threatening condition that manifests through the slow accumulation of abnormal cells in the lungs, resulting in tumors that impair lung function and cause respiratory challenges.”
Olatoke notes that sirolimus, the lone drug approved by the Food and Drug Administration for treating LAM, is not entirely effective and fails to offer a cure. The most critical questions in LAM research focus on the origins of these abnormal cells and their particular attraction to lung tissue. The largest obstacle to discovering a cure for LAM is the incomplete understanding of its fundamental mechanisms.
“A previously unexplored pathway that is dysfunctional in LAM patients has been identified,” says Olatoke. “Two drugs that target this dysfunctional pathway have been found. We are in the process of further evaluating these drugs to ascertain their efficacy in halting the advancement of LAM.”
Upon confirming the dysregulation of this pathway, researchers treated cells from LAM patients and found that the pharmaceuticals were successful in eradicating these abnormal cells. Animal models also supported these findings; treatment with the drugs inhibited the survival and growth of tumor cells within the lungs.
“This research marks a novel avenue of exploration as it has never been previously studied,” Olatoke states. “Our findings suggest that the abnormal cells may originate from the uterus. This is the first empirical evidence indicating a potential link between uterine dysfunction and LAM.”
One fulfilling aspect of the research for Olatoke is the collaboration with LAM patients, particularly noting that June is Worldwide LAM Awareness Month. “The patients are highly empathetic and supportive of our research, even participating in clinical trials. Their willingness to assist makes for an extraordinary community,” she says.
Additionally, Olatoke emphasizes the collaborative nature of the study, involving multiple researchers across different institutions, including the University of Cincinnati, Cincinnati Children’s Hospital Medical Center, and Texas Tech. “The study is a testament to the positive impact of interdisciplinary cooperation in advancing scientific inquiry,” she adds.
According to Olatoke, these findings serve as a preliminary proof-of-concept not only for treating LAM but also for diseases related to tuberous sclerosis complex, a rare genetic disorder causing benign tumors. “The potential ramifications of this research are what drive my continued involvement. The hope is to discover therapeutic strategies that will be beneficial to LAM patients,” she concludes.
Reference: “Single-cell multiomic analysis identifies a HOX-PBX gene network regulating the survival of lymphangioleiomyomatosis cells” by Tasnim Olatoke et al., published on 10 May 2023 in Science Advances. DOI: 10.1126/sciadv.adf8549
