An estimated 12 million U.S. men and women have been diagnosed with Chronic Obstructive Pulmonary Disorder (COPD), which includes conditions such as emphysema and chronic bronchitis and in 2010 surpassed stroke as the third leading cause of death in the U.S. Efforts to identify new treatment approaches are the key to halting this increasingly prevalent disease, which incurred a reported $49.9 billion in related health care costs in 2009.
A new study, led by Daniel Weiss, M.D., Ph.D., professor of medicine at the University of Vermont College of Medicine and a pulmonologist at Fletcher Allen Health Care, was the first-ever clinical trial examining the potential of mesenchymal stem cell (MSC) therapy to reduce chronic pulmonary and systemic inflammation in patients with moderate to severe COPD. The results were published online November 22, 2012 in CHEST, the journal of the American College of Chest Physicians.
“MSCs are stem cells isolated from adult bone marrow, adipose, and other tissues, that in addition to having the ability to differentiate into several specific tissue types can potently regulate inflammation,” says Weiss.
Isolated MSCs, adds Weiss, are not associated with immune system rejection, which allows for safe administration of MSCs obtained from un-related donors. Although the full range of mechanisms of MSC actions on inflammatory processes in different diseases has not yet been fully clarified, there are a growing number of clinical investigations using MSCs in inflammatory and immune-mediated diseases, including multiple sclerosis, type 1 diabetes, and others. Based on the results of these and animal model-based lung disease studies, Weiss and colleagues hypothesized that MSCs would reduce chronic pulmonary and systemic inflammation in COPD patients with corresponding improvement in lung function and in quality of life.
The study was conducted at six sites in the United States including UVM, with Weiss serving as the lead investigator. Participants in the trial received four separate administrations of MSCs or a placebo control and were subsequently followed for two years. A total of 62 patients at the six sites were randomized to double-blinded intravenous infusions of either allogeneic MSCs (Prochymal®, Osiris Therapeutics, Inc.) or placebo control. Patients received four monthly infusions and were subsequently followed for two years after the first infusion. Endpoints included comprehensive safety evaluation, pulmonary function testing, quality of life indicators, including questionnaires, six minute walk evaluation, and assessments of systemic inflammation. According to Weiss, most of the patients enrolled in the study were elderly, had significant lung disease, and also had a number of other medical conditions.
“The study clearly demonstrated safety both during the actual administration of the MSCs, as well as over the two-year follow-up period,” Weiss says. “While there was no obvious efficacy of the MSCs in improving either lung function or quality of life, there were too few patients to accurately assess this. However, the trial’s clear demonstration of safety opens the door to larger trials of MSCs in patients with COPD and also opens the door to investigation of MSCs in other lung diseases.”
Those most at risk for COPD are current and former cigarette smokers. Despite its rising incidence, awareness of COPD has recently dropped to 2008 levels, according to a 2012 report issued by the National Institutes of Health, underscoring a need for improved educational efforts about the disease.
In addition to Weiss, coauthors on the CHEST study include Richard Casaburi, M.D., Ph.D., Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, Calif.; Robin Flannery, Osiris Therapeutics Incorporated, Columbia, Md.; Michelle LeRoux-Williams, Ph.D., Osiris Therapeutics Incorporated, Columbia, Md.; and Donald Tashkin, M.D., David Geffen School of Medicine at UCLA, Los Angeles, Calif.
Several University of Vermont and Fletcher Allen Health Care staff and faculty joined Weiss in playing important roles in the trial, including Vermont Blood Bank members Nella Bartolai-Drexler, Sharon Bushor, Audrey Chafetz, Mark Fung, M.D., Paulette Hammond, and Shelly Hitchcox; Vermont Lung Center staff Stephanie Burns, R.N., Laurianne Griffiths, R.N., and Joan Lippmann, R.N.; and University of Vermont Clinical Research Center members Richard Galbraith, M.D., Ph.D., Joan Bertolet, R.N., Delana Braves, R.N., Betsy Cutler, R.N., Susanna Knoop, R.N., Nanse Nathan, R.N., and Rachel Stringer, R.N.