A collaborative effort between physicians and scientists at the University of Texas Health Science Center in Houston and other centers, has spawned a clinical trial to test a stem cell treatment for stroke patients.
The lead researcher, Sean Savitz, professor of neurology and the director of the stroke program at UT, presented the first results from 10 stroke patients who were treated with stem cells at the World Stroke Congress in Brasilia, Brazil. This clinical trial is the only randomized, double-blind, placebo-controlled intra-arterial clinical trial in the world for ischemic stroke. The goal of this trial is to test the safety and efficacy of a therapy developed by a company called Aldagen Inc. (a wholly-owned subsidiary of Cytomedix Inc.) that uses a patient’s own bone marrow stem cells to treat stroke patients.
In this clinical trial, after a patient has suffered a stroke, the bone marrow stem cells are administered between 13-19 days after the stroke. This therapy, which is known as ALD-401, uses a technology developed and owned by Aldagen to isolate cells from bone marrow that express very high levels of a particular enzyme. This enzyme marks the cells that express it as stem cells. Pre-clinical studies with these isolated cells in mice showed that mice that had suffered from a stroke showed enhanced recovery when given intra-arterial infusions of these stem cells.
All patients infused with these stem cells will be monitored for 12 months after the infusion. The patient’s mental and physical functions will be closely watched, and any side effects from the infusions will be noted and treated.
According the Dr. Savitz, “We have been approved by the Data Safety Monitoring Board (DSMB) to move the study into the next phase, which will allow us to expand the number of sites in order to complete enrollment.”
Since the 10 people treated in this study have not shown any adverse side effects, Savitz wants to eventually enroll 100 patients. According to the submitted protocol for this study, the initial study only placed 10 patients at risk for this untested treatment. Therefore, before more patients could be enrolled in the clinical trial, the Food and Drug Administration had to review the safety data on the first ten patients before more could be enrolled. The FDA has approved the move to the next phase of this clinical trial.
In pre-clinical trials, some of which were conducted at the UTHealth Medical School, bone marrow stem cells promoted the repair of the brain after an ischemic stroke. Savitz and his colleagues induced stroked in rats and measured the amount of oxygen that flowed into the brain by means of Magnetic Resonance Imaging or continuous laser Doppler flowmetry. In rats that made been given injections of bone marrow-derived stem cells, the oxygen flow to the brain was significantly better than in rats that had suffered a stroke but had not been given the stem cell treatments. Savitz’s group also showed that a molecule that dilates blood vessels called nitric oxide was necessary to keep the vessels open and to allow entry of the stem cells into the brain so that they could repair the damage. When Savitz and his group prevented nitric oxide synthesis with an inhibitor called L-NAME, the infused stem cells were unable to enter the brain and fix it, and oxygen flow to the brain tanked. It was the strength of these pre-clinical studies that convinced the FDA to approve this present human clinical trial that tests this same procedure in human patients.
Ischemic strokes result from blood clots in the tiny vessels in the brain, which starves portions of the brain for oxygen, thus killing off brain cells. Stroke is the leading cause of disability in the United States and the fourth most common cause of death, according the statistics provided by the Centers for Disease Control and Prevention in Atlanta, Georgia.