Patients with pulmonary arterial hypertension — high blood pressure in narrowing or blocked blood vessels of the lungs, which can ultimately lead to heart failure — may present similar symptoms, but those symptoms can have vastly different underlying molecular mechanisms. By using patients’ individual molecular profiles, Brown researchers have recently developed a new method to match personalized treatment plans to patients with PAH.
This individualized treatment revealed that aligning information taken from a patient’s cells with a drug’s target was associated with better clinical outcomes.
“Pulmonary hypertension is a complex disease of the heart and lungs,” said principal investigator Corey Ventetuolo, a professor of medicine and of health services, policy and practice, as well as the director of the Division of Pulmonary, Critical Care and Sleep Medicine at Brown University Health and the Warren Alpert Medical School of Brown University.
Navneet Singh, an author on the paper and an assistant professor of medicine, said that PAH “has a very poor prognosis, even with all the advancements that we’ve made over the years with the therapeutics.”
The new system developed by the researchers collects cells from the affected blood vessels at the point of care to build the treatment. Typically, biopsies of affected blood vessels are not taken until the final stages of PAH, Ventetuolo said.
“The thing that we really lack is targeted therapy,” Singh said.
According to Ventetuolo, the goal of the study was to develop a method that would allow clinicians to prescribe individualized treatment for patients — an approach called precision medicine.
Cancer treatment is a good model of precision medicine, Singh said. Cancer researchers often conduct biopsies to understand genetic mutations that help them “target their therapy to that individual’s cancer.”
The data used in the study came from biopsies of patients with PAH. Catheters, which are thin tubes that can be threaded into a patients’ heart and lungs, were used to collect the cells lining the interior of the blood vessels.
“This procedure is required to diagnose pulmonary hypertension, and we do the procedure in a repeated way over the course of the patient’s life with the disease,” Ventetuolo said.
After they collected the cells, the researchers sequenced the cells’ RNA content. Next, they used a bioinformatics pipeline to determine which specific molecular targets are in the patient.
“This study takes an interesting approach by examining molecular interactions in patient-derived cells to better understand these differences and identify potential therapeutic strategies,” Jason Hong — an assistant professor of medicine in the Division of Pulmonary and Critical Care Medicine at the David Geffen School of Medicine — wrote in an email to The Herald. Hong was not involved with the study.
“An important contribution of this work is its potential to move us toward more individualized approaches to treating PAH,” Hong added. “Rather than assuming that the same molecular pathways are equally relevant in every patient, this approach may help identify which therapies are better aligned with an individual patient’s molecular profile.”
According to Singh, the project was a retrospective study where the team looked at previously collected patients’ data. Looking forwards, researchers are interested in a prospective study where the team can recruit a specific cohort.
Ruisheng Wang — co-author and assistant professor of medicine at Harvard Medical School and the Brigham and Women’s Hospital — said that while this study “demonstrates a method that is promising,” she noted that they “need a prospective cohort to further validate the approach.”
Amrita Rajpal is a senior staff writer covering science and research.
