New clinical trial tests efficacy of stem-cell therapy for stroke
By Jack Mazurak
An emergency helicopter trip in May that brought a stroke patient from Forrest General Hospital in Hattiesburg landed the Clarke County resident the first spot in a clinical trial at the University of Mississippi Medical Center for stem-cell therapy.
The new therapy could prevent further brain injury following the initial stroke, preserve vital motor and cognitive abilities and shorten recovery times.
The stem-cell treatment also could add a full day to a narrow four-and-a-half-hour window when current drug treatments work best.
The UMMC Comprehensive Stroke Center is one of 10 U.S. sites enrolling a total of 120 patients into the study. The center aims for about 12 from Mississippi.
Dr. Alexander P. Auchus, professor and McCarty Chair of Neurology at UMMC, serves as principal investigator for Medical Center’s portion of the clinical trial.
“These are pluripotent stem cells derived from adult bone marrow,” Auchus said. “No fetal or embryo-derived cells were used in making this treatment.”
“Pluripotent” means the cells can transform into many different types of tissue: bone, muscle, connective tissue and more. That ability makes stem cells promising for a wide range of medical treatments.
But for biomedical scientists, precise control and manipulation of the cells’ pluripotency has proved difficult in some circumstances.
“All adults have a small amount of stem cells in their bone marrow,” Auchus said. “These were removed from a donor, grown in culture, frozen and distributed to the participating centers.”
Study participants get randomized into either a control group, which receives a harmless placebo, or the test group, which gets the experimental therapy. At UMMC, Bone Marrow Transplant Lab personnel prepare the injections.
“This is a collaboration between many players,” said Tereza Holman, BMT Lab director. “This is more of a straightforward procedure for us than our normal processing of peripheral blood stem cells and bone marrow for transplants.
“But at the same time, a clinical trial like this could not have been done if there wasn’t a lab trained in these preparations.”
Auchus said after a patient consents, the person either gets injected with a placebo or 2.4 million stem cells in solution, all in one infusion, given over an hour. The stem cells circulate through the patient’s bloodstream.
Brain cells in the stroke-injured area deploy signaling molecules known as cytokines that flag down the stem cells. The stem cells – like icing a twisted ankle – may keep the injured brain tissue from inflammation, Auchus said.
“This is not about removing the clot,” he said. “It’s about keeping the brain from swelling, getting irritated and causing further damage as the area deprived of blood flow reacts.”
That domino effect, called an ischemic cascade, can trigger more severe paralysis, speech and cognitive problems and leave the patient weaker and more vulnerable to greater injury or death from another stroke.
Mississippi ranked 46th in the nation for stroke deaths between 2005 and 2007, according to the American Heart Association. With 128,842 lives lost in 2009, stroke continued as the nation’s fourth-leading cause of death behind heart disease, cancer and chronic lower respiratory diseases, according to the Centers for Disease Control and Prevention.
Unhealthy lifestyles, including obesity, tobacco use, hypertension and lack of exercise, contribute to stroke’s likelihood, along with genetic factors.
Stroke remains a frustrating illness for physicians, Auchus said. In standard treatment, patients are assessed in an emergency room, get CT scans from a radiologist and receive a clot-busting medication in consult with a neurologist.
“The only clot-busting medication is FDA-approved for use up to three hours from symptom onset but is commonly used up to four-and-a-half hours from onset,” Auchus said.
If the clot lodges in a reachable blood vessel, neuro-interventionalists can insert an image-guided catheter into the artery to poke, pop or remove the blockage. Catheterization is considered viable for up to about six hours following onset. After catheterization, the patient moves to a neuro-ICU, where specialists treat and monitor progress.
Auchus welcomed new options, saying stem-cell therapy could extend the treatment window to 30 hours after symptoms begin.
Ohio-based biotech researcher Athersys developed the experimental therapy and organized the trial. If this phase II trial proves effective, Athersys will start a phase III trial with about 600 patients.
“They wouldn’t have picked us if we didn’t have the expertise,” Auchus said of the Comprehensive Stroke Center.
Last year the center admitted more than 500 patients for stroke. Regardless of whether patients enroll, and which injection participants receive, all patients get the stroke center’s standard of care, he said.
Study participants receive follow-up MRIs from the Department of Radiology to examine the size of the stroke, and exams for function and strength at seven days, one month, three months and one year.
Auchus said not all stroke patients will qualify for the trial. Among other factors, candidates must have no cancer history, have their spleen and they must be enrolled within 30 hours of the onset of symptoms.
Mississippi’s first participant in the study arrived at Forrest General within two hours of symptom onset, received the clot-buster drug and was transported via helicopter to UMMC, a procedure commonly called “Drip ‘n Ship.”
For those reasons the Clarke County patient was a good candidate, Auchus said. Thanks to UMMC’s AirCare, the patient arrived at the Medical Center’s Emergency Department five hours after onset.
“We considered putting in a catheter but imaging showed us the clot was too far away,” Auchus said. “Although the clot was out of reach, the brain’s reaction to loss of blood flow was still within the realm of treatment.”
The patient, with family support, decided to enroll in the clinical trial. Following standard and trial treatments the patient left the neuro ICU on day three with some minor weakness as the only residual deficit.
“The family was glad to have a center where the patient had options,” Auchus said. “And the patient is home and continues to improve.”