According to Michael Matthay, MD, critical care specialist and professor of medicine and anesthesia at the University of California at San Francisco (UCSF), there are around 200,000 patients per year who have acute respiratory failure in the United States. The mortality rate is around 30 to 40 percent. Matthay and colleagues hope that they will be able to reduce the mortality rate by developing a cell-based therapy.
Matthay and Jae-Woo Lee, MD, Kathleen Liu, MD, MAS, PhD, and Carolyn Calfee, MD, MAS, associate professors of medicine and anesthesia, are working on developing cell-based therapies he hopes will reduce mortality in patients with acute respiratory distress syndrome. This syndrome is a major cause of acute respiratory failure in critically-ill patients.
The group of researchers is working to translate these therapies from concept to clinical practice that is handled by UCSF’s Clinical and Translation Science Institute (CTSI). A series of videos is featured on LaunchPad (online source for translational research). LaunchPad is set up to highlight experiences and accomplishments of UCSF’s translational researchers and to support the development of medical products.
According to Liu, getting a novel treatment into clinical trials requires an “Investigational New Drug” (IND) acceptance from the U.S. Food and Drug Administration (FDA). “Preparing the entire IND application for this project was going to be an enormous undertaking that I think we hadn’t really appreciated.” Fortunately, a colleague of Matthay’s from the University of Texas was able to provide a perfect model system and carry out the experiments in collaboration.
The researchers had worked for many years on pre-clinical studies to support proof-of-concept for stem cell therapies known as mesenchymal stem cells (MSCs). These therapies have the potential to treat injuries to a variety of epithelial organs that include lung and kidney disorders. The Bone marrow-derived MSCs have the ability to release proteins and lipids that have potential anti-inflammatory effects and growth factor ability that appears to enhance lung repair.
So far, pre-clinical information indicates that these cells in vitro and in small and large animal models appears to be working. The problem is to get a source for clinical-grade MSCs. Lui credits “serendipity” and “six degrees of separation” for leading them to a collaborator at the University of Minnesota who creates the cells used in the team’s cell-based therapy. The experience “speaks to how much of science is making connections with people who don’t do exactly what you do,” Liu says.
There have been a number of delays in the research which comes from inexperience regarding the IND process and then following a pre-IND consultation. They found that there was more pre-clinical work that needed to be done using a larger animal model. However, serendipity came into play again as it turns out that a colleague at the University of Texas had a model available and accepted to carry out a collaborative effort.
At this point, Matthay and colleagues have accumulated pre-clinical data and have funding to carry out Phase 2 trials. Unfortunately, the National Institutes of Health Heart, Lung and Blood Institute (NHLBI) that funded the Phase 2 trial does not cover the required Phase 1 trial focusing on safety. Additionally, no trials could be started without IND approval.
As luck would have it, the Catalyst Awards came to the researchers rescue. The Catalyst Awards and their advisor Dave Savello were able to fill in gaps in knowledge and lead the researchers to experts that could aid with the components of the IND they didn’t know how to work with. The Catalyst Awards helped Matthay and Liu to develop a framework for their clinical trials. This led to approval of an IND for a Phase 1 trial. Their first patient was enrolled at UCSF in early July 2013.