A phase 2 clinical trial of new treatment for ischemic stroke derived from a patient’s own bone marrow stem cells has started under the direction of Dileep Yavagal, M.D., assistant professor of clinical neurology and neurosurgery and Director of Interventional Neurology, at the UM Miller School. If proven safe and effective, the cellular therapy, ALD-401, would be the first post-acute treatment for the most common type of stroke, which affects nearly 700,000 Americans annually.
Outside of tissue plasminogen activator (tPA), which must be administered within hours after a blocked artery disrupts blood and oxygen flow to the brain, or the clot-removal surgeries Yavagal performs by threading a clot-retrieval device from the groin into the brain, there are no approved therapies to revascularize vessels after ischemic stroke. Yavagal believes ALD-401, the first proposed stroke treatment to be delivered directly to the brain via the carotid artery within weeks – not hours – after a primary ischemic stroke, may have the potential to be one.
“This is the first intra-arterial stroke stem cell trial in the U.S., which is hugely significant for two reasons,” said Yavagal, who is also Co-Director of Endovascular Neurosurgery and
a faculty member of the Interdisciplinary Stem Cell Institute (ISCI). “First, by delivering the stem cells directly to the brain via the arteries, the cells won’t get trapped in the lungs and liver, which circumvents the problem with stem cells that have been administered intravenously in other trials. And second, laboratory studies have shown these cells decrease stroke damage and improve motor function in animal models – and improving function is our goal.”
Despite the availability of tPA and the minimally invasive intra-arterial clot-retrieval procedures Yavagal performs within eight hours of a stroke to open blocked arteries, less than 40 percent of stroke patients regain their independence. Most live with significant disability, at significant cost.
Known as RECOVER-stroke, the randomized trial with blinded assessments is enrolling approximately 100 participants across the U.S., about 60 of whom will receive an intra-carotid infusion of stem cells derived from bone marrow. The other patients won’t, but will believe they are undergoing an identical procedure. A member of the steering committee for this industry-sponsored multicenter study, Yavagal is actively screening and planning to recruit about 20 patients from the University of Miami/Jackson Memorial Hospital, in partnership with Co-Principal Jose Romano, M.D., professor of neurology and Chief of the Stroke Division in the Department of Neurology, and ISCI.
“With this trial, we are able to bring the most cutting-edge and novel stroke therapy research to our South Florida community,” Yavagal said.
Manufactured by Aldagen, a wholly owned subsidiary of Cytomedix, Inc., ALD-401 is derived from ALDHbr cells isolated from bone marrow and contains all cell types thought to repair and regenerate tissue after an ischemic event. Since ALD-401 offers multiple mechanisms of action on multiple targets, the makers hope it will succeed in restoring functionality where other single-molecule biologics tested in late-stage trials have failed.
Given new research that shows brain inflammation persists for two weeks after a stroke, they also believe ALD-401 will be more effective if administered after inflammation has subsided and the patient has stabilized. As such, patients enrolled in the trial will be dosed 13 to 19 days after their initial episode, with stem cells harvested from their hip and processed by Aldagen 11 to 17 days after the initial episode.
Yavagal’s participation in the RECOVER-stroke trial is an indirect extension of his grant-funded translational laboratory work at ISCI, where he, ISCI Director Joshua Hare, M.D., the Louis Lemberg Professor of Medicine, and other ISCI partners are investigating the intra-arterial delivery of allogeneic bone marrow-derived mesenchymal stem cells to stroke patients. This work is supported by the three-year, $360,000 New Investigator Research Grant Yavagal received in 2012 from the Florida Biomedical Program.