If you are a stroke victim and want to participate in the trial, contact the Chattanooga Center for Neurologic Research, 423-648-0304.
Doctors at Erlanger hospital are looking for stroke victims to participate in a clinical trial of a potentially groundbreaking treatment that could restore movement to paralyzed arms or legs, even as long as five years after a stroke.
Only a handful of stroke victims will qualify for the trial, but the potential is revolutionary, according to Dr. Thomas Devlin, director of the Chattanooga Center for Neurologic Research, which is housed at the hospital and will oversee local patients in the trial.
The trial will involve using a form of stem cell taken from bone marrow that is genetically altered and inserted into a patient's brain in the areas damaged by the stroke.
"To take cells from bone marrow and put them into brain cells is as space-age as putting a man on the moon," Devlin said. "It is as significant as that."
But doctors warn there is no guarantee that the procedure will work or even that the volunteers in the clinical trial will get the treatment.
"We're still in the very early exploratory phases of this type of work," said Dr. Robert Gross, an Emory University surgeon and researcher who is one of several doctors around the U.S. who will perform the operation on the volunteers. "In these cases, a significant area of the brain has been damaged, and simply putting a deposit of undifferentiated cells into the brain and magically thinking they will rewire the brain as good as new is naive. None of us think that."
A previous clinical trial, however, with a small group of only 18 patients, indicated the procedure is safe and appeared to offer some benefit. The current trial, with 156 patients, is intended to fully test whether the treatment works.
If it does, the results could be revolutionary.
A stroke is caused when a blood vessel that carries oxygen and nutrients to the brain either bursts or is blocked by a clot. Without blood and the oxygen it contains, brain cells will die. Strokes are the fifth most common cause of death in the United States, according to the American Stroke Association, killing some 130,000 people every year. They are also one of the leading causes of long-term disability, often leaving victims paralyzed or unable to speak.
Now, strokes can be treated only in a very narrow window of time. There is a drug that will break up the blood clot, but it must be administered within three hours of the stroke, Devlin said. The other treatment is more dramatic — doctors insert a device into the artery that allows them to physically grab the clot and pull it out.
"It is very sexy when we're there at 2 o'clock in the morning and we can go into the brain and it's like the hand of God reaches in and pulls the clot out," Devlin said.
Erlanger was part of a study that showed the clot-grabbing technique, when combined with the drug, dramatically improved patients' chances for survival.
But the clot must be removed within six hours after the stroke or else it is too late to stop the damage to the brain.
A new approach, which was tested in a clinical trial last year in patients from Erlanger and elsewhere using stem cells from the bio-tech firm Athersys, seemed to extend the window for treating stroke victims to as much as 36 hours. In that trial, stem cells were enhanced and then given to stroke victims intravenously — not injected into the brain. Some of the stroke victims showed improved mobility and some restored function.
With the older techniques, "only about 10 percent or less of stroke victims got to the hospital in time to be treated," said Dr. Gil Van Bokkelen, chairman and CEO of Athersys. But by extending the time for treatment to 36 hours, "we could treat 90 to 95 percent of patients," he said.
The initial results seem to show that five times the normal number of stroke victims achieved a full recovery. A second, larger trial is ramping up to try to replicate the results of the first trial.
"If we can validate the results we have seen from this trial, it could redefine stroke treatment," Van Bokkelen said.
The products used in last year's Athersys trial and in the upcoming trial, with the bio-tech firm SanBio, are an altered or enhanced form of stem cell that is taken from bone marrow.
Stem cells have fascinated medical researchers because, unlike normal cells, which have a specific function, they all have the ability to be reprogrammed to perform a different function by inserting additional genetic material.
Bio-tech companies have raced to patent their own particular modifications and then conduct trials to prove their usefulness.
A type of cells from bone marrow, stromal stem cells, normally secrete certain chemical compounds useful in the bone, but can be modified genetically to secrete other compounds that may be useful in the brain, for example. In the Athersys clinical trial, doctors believe the cells secreted something that improved the body's ability to counteract the effects of the stroke.
Inflammation was reduced in the brain, more new blood vessels seemed to grow, and connections among neurons in the damaged brain were boosted.
"By increasing the connections between the neurons that are left, it helps rewire the brain in a very powerful way," Devlin said.
But even if that approach works, it is only useful in the first 36 hours after a stroke. Erlanger's latest clinical trial hopes to extend the time in which stroke victims can be treated exponentially, from 36 hours to as long as five years.
And in this trial, the stem cells will be injected directly into the damaged areas of the brain.
Doctors will first do a special MRI scan of the patient's brain to determine exactly where the tissue damaged by the stroke is located. Then a surgeon will drill a half-inch hole through their skull just above the damaged area, and stem cells will be injected directly into the brain.
The trial will use genetically altered bone marrow cells patented by the California-based bio-tech company SanBio.
The first test showed promising results, but the sample size was small, only 18 people, and there was no control group, or group of people who did not get the treatment. Emory's Gross emphasized that neither the patients nor their doctors need to know whether or not they actually receive the treatment. Previous studies have shown that if patients know they were given the treatment, they will tend to say they believe it helped them, whether it actually did or not.
In the new study, if patients are in the control group, small holes still will be drilled into their skulls, but nothing will be injected into their brains, Gross said. After the operation, "if they were to feel up top, they would not be able to determine that they didn't get something done," he said.
One-third of the patients will get a dosage of 2.5 million altered cells, another third will get a dose of 5 million cells, while the final third will be in the control group and get nothing.
After several months, doctors will give all of the patients a series of tests to measure their mobility and brain function.
The results from the first test were promising, despite the small sample size.
"In a subgroup of patients we saw a very dramatic improvement," said Dr. Damien Bates, chief medical officer and head of research for SanBio. "Patients who were bed bound were able to get out of bed, and patients who were not able to raise their arms were able to raise them above their shoulder."
"We think that the cells when you inject them don't last long, but they stimulate a patient's own body to repair itself," he said.
But Gross was more wary.
"It is important not to get too far along on the hype curve," he said. "There was an indication there might have been some positive benefit, with the complete understanding that this benefit might have been derived from the placebo effect."
The placebo effect is when patients appear to get better if they believe they have been given a treatment, even if they actually are given a sugar pill that contains no drug.
While Erlanger's Devlin is looking for volunteers for the trial, only a handful will meet the difficult criteria to be selected. Patients must have had a stroke more than six months but less than five years earlier, and should be suffering some paralysis. But they must also not suffer from any other disease, have a life expectancy of several years, and be in generally good health, with no substance abuse problems.
While he is excited about the upcoming research, Devlin understands the odds that the early promise won't be fulfilled or that an unexpected side effect may limit the treatment's value. But after decades of seeing stroke victims with little chance for recovery, he is optimistic that new options are on the horizon.
"We deal with people on the worst day of their life all the time," Devlin said. "What you're able to give these people that they have not had is hope. It's really amazing to see that."
Contact staff writer Steve Johnson at 423-757-6673, firstname.lastname@example.org, on Twitter @stevejohnsonTFP, and on Facebook, www.facebook.com/noogahealth.
This story was updated Sept. 19 at 8:45 p.m. for clarification of terms.