An estimated 200,000 patients a year have acute respiratory failure in the U.S. and mortality is about 30 to 40 percent, according to Michael Matthay, MD, a critical care specialist and professor of medicine and anesthesia at UC San Francisco.
Matthay is working with Jae-Woo Lee, MD, Kathleen Liu, MD, MAS, PhD, and Carolyn Calfee, MD, MAS, associate professors of medicine and anesthesia, on developing cell-based therapies that he hopes “will make a major difference in reducing mortality in patients with acute respiratory distress syndrome, a major cause of acute respiratory failure in critically-ill patients.”
LaunchPad, a project of UCSF's Clinical and Translational Science Institute, is designed to highlight the experiences and accomplishments of UCSF’s translational researchers, and to support them in their efforts to develop beneficial medical products.
The research team’s experience translating these therapies from scientific concept to clinical practice is featured in a series of videos on LaunchPad, a new online resource for translational researchers that is managed by UCSF’s Clinical and Translational Science Institute (CTSI).
Moving a novel treatment into clinical trials requires an "Investigational New Drug" (IND) approval from the U.S. Food and Drug Administration (FDA). As Liu describes in the video, “Preparing the entire IND application for this project was going to be an enormous undertaking that I think we hadn’t really appreciated.”
Up until the IND process, the team of investigators had worked over many years on pre-clinical studies supporting proof-of-concept for a therapy using a type of stem cells, known as mesenchymal stem cells (MSCs), that could potentially treat injury to a variety of epithelial organs, including the lung and kidney.
Bone marrow-derived MSCs release proteins and lipids with potent anti-inflammatory effects as well as other growth factors that seem to enhance lung repair. Favorable pre-clinical data using these cells to treat injured lung tissue in vitro and in small and large animal models encouraged them to move into clinical trials. The struggle to implement this potentially life-saving therapy began with a search for clinical-grade MSCs. Liu 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.
Identifying Gaps in the Development Plan
Matthay admits being naïve regarding the IND process, and following a pre-IND consultation, the investigators discovered that there was additional pre-clinical work to be done using a larger animal model. Matthay says that serendipity again came into play as a colleague at the University of Texas had the perfect model system available and agreed to carry out the experiments in collaboration.
Matthay and his colleagues have amassed a body of compelling pre-clinical data and secured funding to carry out phase two trials. However, 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. Furthermore, no clinical studies could be initiated without an approved IND.
It was at that point that the Catalyst Awards, another program managed by CTSI, “came to our rescue,” says Matthay. Liu echoes the sentiment, explaining that the Catalyst Awards and their advisor Dave Savello “were instrumental in helping us identify our knowledge gaps, and identify individuals and experts who could help us with those components of the IND that we simply don’t have the expertise to do.”
The Catalyst Awards provide expert feedback and funding to accelerate translational research into marketable products. Regulatory consultants helped Matthay and Liu develop a solid framework for their clinical trials, guiding them towards operationalizing the details of the design. This additional support led to the approval of an IND for the Phase 1 trial of this exciting new therapy, which enrolled its first patient here at UCSF in early July of this year.
UCSF's CTSI is a member of the Clinical and Translational Science Awards network funded through the National Center for Advancing Translational Sciences (grant Number UL1 TR000004) at the NIH Health. Under the banner of "Accelerating Research to Improve Health," CTSI provides a wide range of resources and services for researchers, and promotes online collaboration and networking tools such as UCSF Profiles.