UC Davis Health System researchers working to speed therapies to patients suffering from critical limb ischemia (CLI) received approval today for a $14.1 million grant from the state's stem cell agency, the California Institute for Regenerative Medicine (CIRM). The funding is specifically designed to lead to U.S. Food and Drug Administration approval of human clinical trials using stem cells and regenerative therapies.
John Laird, professor of cardiovascular medicine and director of the UC Davis Vascular Center, is leading a team that plans soon to begin testing stem cell therapies for peripheral vascular disease, which affects about 2 million people around the country.
CLI is caused by severe artery obstructions, which result in a critical reduction in blood flow to the feet and legs. It occurs most commonly in individuals with diabetes and severe peripheral artery disease. The condition is associated with pain, debilitating foot ulcers, gangrene, and increased risk of leg amputation and death. Despite the best revascularization efforts, effective therapies often do not exist for CLI at its end stages.
Bolstered by recent preclinical studies that demonstrated stem cell treatments are safe and effective for the disease, Laird and his co-principal investigator, Jan Nolta, professor of internal medicine and director of the UC Davis Institute for Regenerative Cures, plan to use mesenchymal stem cells from healthy bone marrow donors that are bioengineered to produce a revascularizing factor. The cells will be injected into the legs of CLI patients and are expected to migrate to oxygen-low areas of in the patient's diseased limbs.
"Our combination stem cell strategy is analogous to a paramedic vehicle that can deliver emergency care directly to a patient," said Laird, who has been investigating different stem cell approaches as possible vascular therapies for several years. "We've seen that the special growth factors produced by our engineered stem cells, can rapidly restore blood flow in the limbs of animal models that had no leg circulation whatsoever. Our CIRM grant now enables us to completely focus on finalizing safety and efficacy tests for humans so we can move this candidate therapy into clinical trials that will hopefully save people from amputation."
The UC Davis team is collaborating with researchers at Reina Sofia University Hospital in Cordoba, Spain, to develop the novel therapy. The international effort is a part of the Andalusian Initiative for Advanced Therapies, which was created by the regional government of Andalusia to sponsor non-commercial clinical trials in the field of cellular therapy.
"Critical limb ischemia represents a significant unmet medical need in the U.S. and around the world," said Nolta, who directs the overall stem cell program for UC Davis. "We know that sophisticated catheters, stents and bypass surgeries don't work at the end stages of the disease. Having colleagues in Spain also working on this debilitating condition complements our research and helps all of us move much more rapidly toward developing a good and effective therapy."