Atlanta, Georgia -- Imagine having your back cut open, part of your spine removed, a stabilizing device that resembles a mini oil rig mounted on your back, the outer membrane of your spinal cord sliced open and experimental stem cells injected into it -- all for the advancement of science because it's not expected to benefit you.
John Cornick, 51, did just that earlier this month as part of a groundbreaking clinical trial.
Almost a year ago, Cornick was told he had ALS -- better known as Lou Gehrig's disease. The diagnosis left him "fairly devastated," he says.
He knew the prospects were grim because there is no cure.
But John wasn't giving up so quickly, nor was his wife, Gina.
"I knew he was a fighter from the beginning and he really wanted to do something," Gina Cornick says. She found information about a clinical trial on online and immediately signed him up, even though she had no idea where it was being held.
ALS destroys the nerve cells in the brain and spine which control muscle movement. When the brain can no longer tell muscles to move, they eventually die, depriving the patient of the ability to move arms and legs and eventually breathe.
The goal of this phase 1 trial is to determine whether fetal stem cells can safely be injected into the spinal cord. Ultimately, researchers hope to show that these cells may slow or halt the progression of the fatal disease.
But for now, the only goal is establishing safety.
Clinical trial
The Cornicks live in North Carolina, just a few hours from Atlanta, Georgia's Emory University, the site of the trial. It is the first FDA-approved clinical trial to inject fetal stem cells directly into the spinal cord of an adult.
Dr. Jonathan Glass, director of Emory's ALS center, is overseeing the trial. Cornick and two previous patients in the trial are heroes, says Glass, because at this point, the trial will likely produce only information, not results.
"In reality what do these patients have? Time, families and their life and we're putting all of these at risk," says Glass.
Dr. Lucie Bruijn, science director of the ALS Association, says the progress being made in this clinical trial is exciting. "We've been able to move it forward ... from animal testing now into actual patients." The treatment had not been tried in humans before.
Glass hopes this trial will lead to a new form of treatment for people with ALS. "We're testing multiple things: We're testing the safety of the surgery; we're testing the cells; we're testing immunosuppressants[because scientists do not know whether the body will reject the cells]." They are also testing how well Cornick handles this major surgical procedure, says Glass.
"After we're finished with the first 12 or 18 patients we will know whether this is surgery that patients can tolerate."
As he was prepped for surgery, Cornick was hopeful but realistic. "Well, of course you'd like to get up and walk ... but I know that's not going to happen."
Stem cells
The stem cells used in the surgery are shipped overnight from Maryland, where Neuralstem, the company funding the trial, is based. The stem cells' source is donated tissue from the spinal cord of an 8-week old aborted fetus, which was donated to the company. The company has developed a method that enables growth of millions of stem cells from this single source of human nerve stem cells.
Before the surgery can begin, a technician at Emory has to verify that a majority of stem cells made it to Atlanta alive. At least 70 percent have to be viable. In this case three samples under the microscope showed 85 percent of the cells arrived alive.
Lead researcher Dr. Eva Feldman, a neurologist at the University of Michigan, designed the trial just four years ago. After a lot of animal testing, her team determined that using fetal nerve stems rather than human embryonic or adult stem cells (such as bone marrow stem cells) was most effective, she says.
Stem cells have the ability to turn into different cells in the body. However, human embryonic stem cells, which come from 4- or 5-day-old embryos, also been found to sometimes turn into cancer cells. Fetal stem cells, such as those used in this trial, are a few weeks older and have already taken on a specific identity -- in this case nerve cells.
Feldman says the fetal stem cells used in this trial did not become any of the unwanted cell types. "That's very, very important," she says.
Surgery
Animal testing also proved very useful when it came to figuring out how to actually inject the stem cells. Emory University's neurosurgeon Dr. Nicholas Boulis invented the device that holds the needle that injects the stem cells. The goal is to inject the cells without injuring the spine and causing even more paralysis. He practiced on 100 pigs before attempting the procedure on a human.
Boulis says it's critical that the injection be done in a very slow and controlled way.
"If you inject quickly, you're going to create pressure at the head of the needle and that can cause damage," Boulis says. That pressure can also inflate an area in the spinal cord which could cause the stem cells to seep back out of the cord when the needle is pulled out, he says. "So by pumping [cells] in slowly you have more security that you are not going to have reflux and you're not going to have damage."
Dr. Jeffrey Rothstein, who heads the ALS research center at Johns Hopkins University and is not connected to this trial, said work on this method is a big achievement. "This is purely about how to surgically deliver cellular therapy to spinal cord," he says. "It's never been done before."
After the spinal cord was exposed, the injections began. Cornick got five -- each one contains about 100,000 stem cells.
The four-and-a-half hour surgery went smoothly, Boulis, says. "There were no surprises."
Post-surgery
A day after surgery, Cornick was lying flat in a hospital bed, chatting and laughing with some friends from North Carolina.
One week after surgery, he says he felt amazingly well and was still hopeful the cells would do some good for him.
Two weeks later Cornick's stitches were removed and he was able to drive home. But he will be making frequent visits back to Atlanta as Glass and his team continue to monitor him.
Neuralstem's Chief Scientific Officer Karl Johe says after the trial's safety board reviews all existing data, including Cornick's results, a fourth patient can be treated with the stem cells.
"Patients Four, Five and Six will receive twice as many [stem cell] injections," Johe says. They will get five more injections on the other side of the spinal cord compared with Cornicks's surgery.
Cornick expects the researchers will follow his progress for a long time. He says he understands the need for people to be willing to participate in experimental research like this.
"For me it just seemed like the right thing to do. I almost felt I had an obligation to do this," he says. "To help other people and myself."
