Back in 2013, I wrote a blog post that has received more comments and requests for updates than any other story I’ve written. The piece highlighted a Stanford-led study that explored the possible causes of pulmonary hypertension, a disease characterized by dangerously high pressure in the lungs.
What made this story so special and — more importantly — what’s the latest on this research? To find out, I recently met with the study’s senior author Mark Nicolls, MD.
The current treatments for pulmonary hypertension focus on dilating pulmonary blood vessels to alleviate pressure in the lungs, Nicolls told me. This treats a symptom of the disease, but not the underlying cause. To address this gap in knowledge, Nicolls; first author Wen Tian, PhD, and his team explored the possible causes of pulmonary hypertension and tested whether a drug, called ubenimex, could effectively treat the source of the disease.
They found that the abnormal cells in pulmonary arteries — a hallmark of pulmonary hypertension — are caused by an inflammation-producing molecular pathway. When rats with induced pulmonary hypertension were treated with ubenimex, the disease reversed.
The next step was to bring the study to clinical trials. This process can sometimes take years, but with the aid of Stanford's SPARK program and the Vera Moulton Wall Center, Nicolls' team was able to embed the research project with the company Eiger within months. This enabled them to begin clinical trials quickly.
“I’ve been told this was is one of the fastest rat-to-man transitions anyone had seen," Nicolls said. "We were lucky with this trial because the drug, ubenimex, has been used in 100,000 Japanese patients already and it’s safe and well tolerated… It just had never been used to treat pulmonary hypertension."
“Stanford is highly supportive of translating its discoveries into new therapies for the benefit of the common good,” Nicolls said. "If I as an investigator didn’t have that support, it’s very hard to imagine how this would have happened.”
Nicolls is now an advisor to Eiger, which will shepherd this clinical trial through to completion, and ubenimex is currently being tested on patients with group 1 pulmonary arterial hypertension. There are many types of pulmonary hypertension so "there's room for multiple types of therapies in the future," Nicolls told me. "I foresee a precision medicine approach where patients will have different cocktails of drugs layered on depending on the type of pulmonary hypertension they have."
This clinical trial is still accepting patients; pulmonary hypertension patients who would like take part can learn more by visiting the clinical trials website.
Previously: Another piece of the pulmonary-hypertension puzzle gets plugged into place, New arterial insights portend potential treatments for life-threatening diseases, A doctor's journey from Iran to the United States and A story from the edge of medical possibility: Operatic soprano sings after double lung transplant
Image by Carla Arenas