Brain & Nervous System Health Center

Stem Cells for ALS: Inside a Clinical Trial

ALS Patient Volunteers for Stem Cell Transplants Into Spinal Cord

From the WebMD Archives

John Jerome's spinal cord shines white beneath the surgeons' headlamps, crisscrossed by a web of bright-red blood vessels. He's been on the operating table for more than four hours.

Above the fist-sized opening in his neck hangs a complex steel contraption. It's fixed in place by four posts: two wedged into Jerome's skull and two more in the vertebrae below the surgical wound. Invented by Emory neurosurgeon Nick Boulis, MD, it serves a single purpose: To hold steady the thin needle plunged into Jerome's spinal cord. If it breaks, it could kill him.

A thin tube runs from the needle through the device and over to a small nearby table. At the table, concentrating intensely, Jonathan Glass, MD, is pumping stem cells into the tube from a small vial. On huge high-definition monitors, magnified images show Boulis plunge the needle directly into Jerome's naked spinal cord. The tube flexes. The doctors, nurses, technicians, and observers in the room hold their collective breath.

Glass counts down the time left in the infusion. Nobody speaks. The needle comes out. Boulis moves it a few millimeters, and coaxes it back into the spinal cord. Another vial of stem cells starts trickling through the tube.

A Deadly Disease

The journey that landed Jerome on that operating table started with a marathon. Like many runners training for a marathon, Jerome felt something go wrong with his stride -- and then there was this pain in his left knee. He underwent knee surgery, and the doctors told him the strength in his leg would return to normal.

It didn't. A year later, the same thing happened with his right leg. Over the next months Jerome's balance became less steady. And then his speech got noticeably slower. He checked his symptoms on WebMD. Then he made an appointment with a neurologist. He asked his wife, Donna, to come along.

"While he was doing some tests, he was kind of going, 'Mmmmm...,'" Jerome, 50, recalls, making that dreadful moaning sound you never want to hear from a doctor. "Then he goes, 'Well, I believe you have ALS, Lou Gehrig's disease .' I knew from going on WebMD I might have it. I hoped not. But that wasn't the case. It was devastating." He was 41 years old at the time.

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Amyotrophic lateral sclerosis (ALS) is the disease that struck down baseball great Lou Gehrig and now bears his name. It's better understood as motor neuron disease , because these are the cells that waste away or die. They stop sending messages to the muscles. Eventually, the muscles that control breathing no longer work.

Neurologist Jonathan Glass now has treated about 2,000 ALS patients. He's writing a paper on what he's learned from the first 1,200 who died. He recently told a 45-year-old man with two teenage kids that he was going to die. For Glass, this was not an unusual day.

"I have been doing this a long time. I still have to tell patients every day, 'I can't cure your disease,'" Glass says. "They come to you and say, 'Doc, what can I do about this?' And I say, 'We are trying. We are trying.' But we don't have a clue what causes this disease. Not a clue."

ALS is always fatal, usually within three to five years. About a quarter of patients survive longer than five years. John Jerome got his ALS diagnosis more than nine years ago. He can still walk, with the help of leg braces and a walker. He can still talk, albeit with difficulty. He can still breathe.

"I have really outlived most people with ALS, so I am grateful," Jerome says. "After some crying, Donna and I got ourselves together and told the family. It was a hard thing to do but we made it through. ... We have come together as a family and learned to adapt. We are doing great."

That kind of attitude makes ALS patients "the best patients in the world," Glass says. "These are big boys and girls. If you know what they've got, you tell them. But the next thing you tell them is, 'I am going to take care of you.' They need to know you care. They want you to listen to them, and to know that no matter what happens you will be there to help them. And if you can't, don't lie to them."

Glass asks all of his ALS patients to donate their brains to science so that researchers can one day find out exactly what it was that caused their disease, and their deaths. In Jerome's case, he asked one thing more.

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Stem Cells for ALS

Jerome lives in Auburn, Ala., but has been making the two-hour drive to Glass' ALS clinic at Emory in Atlanta every six months since 2003.

The day before his surgery, he's been put through a full day of tests: muscle function tests, mental tests, blood tests, heart and lung tests, the works.

"It was in March of 2011 when they approached me about doing this clinical trial. I said yeah, I'll do it," Jerome recalls. "I mean, why not?"

There are plenty of reasons why Jerome might not want to participate. Even patients who know they are dying have a lot to lose. Precious months of life can be lost. Efforts to slow disease can backfire, making patients much worse much faster. And when surgery is involved -- particularly surgery not just on the spine but on the spinal cord itself -- there's a very real risk of death.

Why would Jerome risk everything he and his family still had? The magic words "stem cell."

Type those words into an Internet search engine and you'll find dozens of clinics offering stem cell cures for nearly every chronic disease on earth, including ALS. Some shady clinics profit from the hopes raised by the central role of stem cells in regenerative medicine. Real stem cell research, however, is moving at the slower pace that science demands.

"People travel around the world to get 'stem cell' treatment," Glass says. "So unless we prove it works or it doesn't, people with no other options will pay large sums to get this. And that is wrong."

Glass suspects that the nerve wasting in ALS involves an unhealthy environment in the tissues surrounding nerve cells. Part of that unhealthy environment may be the excess of a DNA building block, glutamate, in the brains and spinal cords of ALS patients. Another part may be that cell signals supporting nerve health may be lost.

Neural stem cells -- stem cells committed to becoming part of the nervous system but still able to become different kinds of nerve cells -- might be the answer. These stem cells produce a "glutamate transporter" that carts off excess amino acid. And they also emit growth signals supporting nerve growth.

"These stem cells, I believe, are nurse cells," Glass says. "They are going to create the needed cells that are going to be supportive to the motor neurons."

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Stem Cell Clinical Trial Breaks New Ground

The sponsor of the clinical trial, Neuralstem Inc., has found a way to grow neural stem cells and to freeze them until they are ready for use. University of Michigan researcher Eva Feldman, MD, PhD, had the idea to infuse the cells directly into the spinal cords of ALS patients. She got FDA permission to try it on patients.

This meant asking patients to undergo surgery to remove the bone surrounding their spinal cords. It meant asking them to take immunity-suppressing drugs for the rest of their lives, to prevent rejection of the new cells.

And it meant asking them to do something never before attempted in living people: direct infusion of stem cells into the spinal cord.

Emory's Boulis was the surgeon Feldman entrusted with this job. And Glass' ALS clinic at Emory offered a ready pool of patients and doctors able to participate.

The FDA insisted that they take things one step at a time. Glass feels the agency is being overcautious given that ALS patients already face certain death. The FDA's position is that safety is paramount, and that baby steps are less risky than giant leaps.

The first ALS patients in the trial were on ventilators because they'd already lost the ability to breathe and to walk. They received infusions only on one side of their lower spinal cord. Next came patients able to breathe, followed by patients able to walk. Then both sides of the lower spinal cord were infused. Jerome was one of those latter patients.

But the motor neurons that control breathing -- the ones ALS patients need in order to survive -- are in the upper spinal cord, in the neck. The next step of the study would be to put stem cells not only in the lower spine, but also in the upper spine. The first three patients to undergo this operation would get the cells only on one side of the upper spinal cord.

Jerome volunteered a second time.

"I think of it being like a soldier who has done one tour of duty re-enlisting for a second tour in order to serve his country," Donna Jerome says.

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"Yes, they did tell me about the risk," John Jerome says. "I am not one who is going to go out and raise millions of dollars for research, but I wanted to do something. This is my way of giving back. If it doesn't work for me, maybe they will learn and help others down the road."

Jerome may well benefit. And he might not. This is what researchers call a phase 1 study. The first goal is to demonstrate that the stem cells can be infused with relative safety. Patients will be followed to see whether their disease slows or improves. But only the last three patients in the study will get the full dosage of 10 stem cell infusions on both sides of their upper and lower spinal cords.

Jerome is not in this final stage of the study. He got five infusions on each side of his lower spine and five on one side of his upper spine.

"I don't want to get my hopes up too much. But I'd be lying if I said I didn't want it to work," he says. "It didn't work the first time, and the immunosuppressant drugs gave me a bad time. In the back of my mind I want it to work, but mostly I want to help other people with ALS and further the science."

Will Stem Cells Help ALS?

On the big screens in the operating room, the magnified image reveals delicate threadlike nerves sprouting from the side of Jerome's spinal cord. These are the sensory nerves that bring information about the outside world into the spinal cord and up to the brain .

Deeper down, out of sight, motor nerves emerge from the cord. These are the nerves that Jerome desperately needs to stay alive. These are the nerves the stem cells are supposed to protect.

Boulis moves the needle again and places it in the spinal cord for the fifth and final time. This time it nicks a tiny blood vessel, and there's a small amount of bleeding. That happens in about one in 10 injections, Boulis says. It's a worry, but a small one, and the infusion continues until Glass calls time.

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Over the next hours, with the dance beats of Beyonce and Black Eyed Peas booming from Boulis' playlist, the surgeons will wire Jerome's spine back together, inserting screws and plates to hold it secure. Then they'll close the wound, leaving behind those five stem cell infusions.

"There is fairly good data that these cells integrate into the rat spine and regenerate motor nerve cells. Does this happen in humans? I don't know," Glass says. "We've done four autopsies in the trial so far. We are having a lot of trouble finding the cells or finding where they are reconnecting nerves."

On the other hand, these were among the sickest patients in the trial. And there's some early clinical evidence that gives Glass, Feldman, and Boulis "cautious optimism" that the treatments have slowed ALS progression in at least one patient.

Glass is careful not to raise false hopes. But he's already had to turn down many ALS patients who did not meet the strict entry criteria for the clinical trial.

"Some people get mad; some have offered lots of money. But if we don't stick to our protocol, we will never know if it works or not," he says. "My goal is to find new treatments for ALS. If it is not stem cells, fine. I will find something else. Something that works."

Glass admits that he has his bad days.

"One thing I don't do is go to funerals. I can't," he says. "These people become very close to you, and their families become very close to you. I lose too many."

Jerome knows that what he's suffered in this clinical trial may ultimately do him no good.

"I'm not a hero," he objects. "Anybody with ALS would do it, 99 out of 100 of us. I am not a hero. I'm just trying to move science forward."

A month after the surgery, Jerome says that he may be seeing one area of improvement in his ALS.

"Maybe my speech might be a little bit better. I can say some words easier than I did before. My wife, Donna, thinks so and one of the nurses at Emory even mentioned it," Jerome says. "But they won't know if the stem cells survived and did anything until I die and they do an autopsy."

Jerome laughs. "I'm hoping that's maybe 30 years from now."

WebMD Feature Reviewed by Laura J. Martin, MD on July 17, 2012

Sources

SOURCES:

John Jerome, Auburn, Ala.

Donna Jerome, Auburn, Ala.

Eva Feldman, MD, PhD, professor of neurology, University of Michigan, and president, American Neurological Association.

Nicholas Boulis, MD, neurosurgeon, Emory University Hospital.

Jonathan Glass, MD, professor of neurology and neuropathology and director, Emory ALS Clinic, Atlanta.

National Institutes of Health web site.

Neuralstem web site.

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