by +Richard Holbrooke – UM Miller School professor of medicine and surgery Marilyn K. Glassberg, M.D., has won approval from the U.S. Food and Drug Administration to conduct the first U.S. clinical trial of mesenchymal stem cells as a potential therapy for patients with idiopathic pulmonary fibrosis.
Issued 30 days after she applied for an investigational new drug trial, the FDA approval gives Glassberg her first real hope of extending or improving the lives of patients with the progressive and fatal lung disease that has no known cause or treatment, other than a risky transplant. About half the patients die within five years of diagnosis.
“Most of these patients walk into my office with their burial plots ready to go, and want to know how many more months they have,” said Glassberg, who has conducted most of the available studies on potential therapies for idiopathic pulmonary fibrosis. “Wouldn’t it be nice if I could say, ‘You know what? You’re going to get a lot more months now.’ If stem cells work, it’s a new lease on life.”
Joining Glassberg in testing the therapeutic potential of intravenous mesenchymal stem cells for the disease characterized by progressive shortness of breath and irreversible loss of lung function is Joshua Hare, M.D., the Louis Lemberg Professor of Medicine and Director of the Interdisciplinary Stem Cell Institute (ISCI). Glassberg’s application to the FDA, which authorized a Phase 1 trial with nine patients who will receive escalating intravenous doses of donor mesenchymal stem cells during a brief hospital stay, was inspired by Hare’s pioneering research in cardiac stem cell therapies. While reading his 2009 study in the Journal of the American College of Cardiology that demonstrated the capacity of mesenchymal stem cells to repair hearts damaged by myocardial infarction, she was struck by one of its findings: mesenchymal stem cells infused into the heart noticeably improved lung function, too.
Curious about the extent, she contacted Hare. When the pair met, they discussed the available cardiac data, and the fact that the lungs are the first stop for injected stem cells. It didn’t take long for the researchers to agree they should try stem cell therapy for the desperate pulmonary disease that has frustrated Glassberg for more than a decade.
“It is well documented that the cells go to the lungs first before passing into the heart. That is the reason we decided to try it,” she said. “We think they could provide factors that are needed to stimulate other cells into making new tissue. The lung can’t repair itself so that is the only hope.”
Calling idiopathic pulmonary fibrosis (IPF) “dreadful,” Hare said the disease “seems to have all of the features and characteristics that would make it responsive to cell therapy. And since we have very significant experience with these cells, and understand their safety profile, dosing and manufacturing, it seemed very worthwhile to partner with Marilyn to come up with this very exciting program of cell therapy for IPF.”
The FDA and the NIH apparently agree. With vital assistance from ISCI’s investigational new drug team and Rebecca Toonkel, M.D., a senior pulmonary fellow at the time, all the necessary application documents, including Glassberg’s previous IPF studies and ISCI’s extensive experience with mesenchymal stem cells, were assembled and submitted.
The proposal quickly passed ISCI and FDA reviews. Concurrently, the NIH’s National Heart Lung and Blood Institute convened a comprehensive review of all issues of cell therapy in lung diseases and invited Glassberg and Hare, along with other national experts, to attend the November 13-14 meeting of its new working panel.
The researchers also plan to submit an RO1 grant proposal to the NIH for the second phase, a double-blind, randomized study of 16 patients. With the nine patients already pre-screened, Glassberg hopes to complete the first phase within six months of Institutional Review Board approval.
“After 10 years, nothing has worked and it’s been really sad,” she said. “But, finally, I have a lot of hope for these patients.”