Neuralstem in the News
Operation marks another step forward in stem cell research
- For the first time, stem cells are injected into the spinal cord in the neck
- It is part of a trial to see if the procedure can be safely done
- "I feel like we finally arrived," says the surgeon who invented a key structure
Atlanta (CNN) -- A 50-year-old man from Trion, Georgia, is the first person to be injected with stem cells in the upper part of the spinal cord, making him yet another pioneer in the scientific quest to use stem cells to heal.
Richard Grosjean received the treatment Friday. He is part of an ongoing FDA-approved clinical trial that is testing the safety of injecting stem cells into the spinal cords of patients with amyotrophic lateral sclerosis, or ALS, also known as Lou Gehrig's disease.Grosjean was diagnosed a little over two years ago, his wife, Tracie, told CNN. He can still walk with a cane, but he has a lot of weakness on his left side and has trouble with his speech.
"I'm pretty much his voice for him," Tracie Grosjean said.
Through his wife, Grosjean says "he has 100% confidence in Emory and Dr. (Jonathan) Glass and Dr. (Nicholas) Boulis and the good Lord that good things will come" from the trial.
While the Grosjeans know this procedure is likely to be more helpful to others in the future who have to deal with this "horrible disease," they have hope and faith that some good will come of this for them, too. In addition to praising Emory University, Tracie also praises her husband's employer, Mount Vernon Mills, which she says has "bent over backwards" to keep him employed throughout his illness giving him a sense of purpose.
The cause of ALS is unknown, but the disease is fatal because nerve cells, or neurons, in the brain and spinal cord needed to tell muscles to move, waste away or die. Early in the disease, patients have difficulty speaking and walking, both symptoms Grosjean now has. Eventually, the disease cuts off communication between the brain and chest muscles, so patients can no longer breathe.
Most people die from respiratory failure, according the National Institutes of Health, and most patients die within three to five years of diagnosis.
The team of researchers in this clinical trial is headed by University of Michigan neurologist Dr. Eva Feldman, who designed the trial; neurologist Glass, who is in charge of the clinical trial at Emory University in Atlanta, where patients are getting the injections; and Emory neurosurgeon Boulis, who invented the structure used to safely inject the stem cells into the patient.
In an operation than lasted about four hours, Grosjean received five injections into the cervical, or neck, area of his spinal cord, each delivering 100,000 cells. The cells came from Maryland-based biotech company Neuralstem, which is funding this clinical trial and devised a procedure to grow millions and millions of motor neuron cells from the donated spinal cord tissue of an 8-week-old aborted fetus.
These are not embryonic stem cells, like the ones used by California-based company Geron, which has injected cells grown from human embryonic stem cells into the spines of at least four patients with complete spinal cord injuries.
Embryonic stem cells have the ability to become any type of cell in the body. One week ago, Geron decided to stop their trial because it was too expensive to continue.
The cells in this ALS trial were taken from the spinal cord of the fetus, so they have already gone down the path of becoming nerve cells. Researchers are hoping to show that injecting neural stem cells -- the precursors to nerve cells -- into the spinal cord of ALS patients is safe.
Ultimately, the hope is that by injecting the cells into the neck, above the lungs, where the mostly deadly damage is done by ALS, these neural stem cells will reconnect communication from the brain to the muscles, keeping patients alive longer and maybe, one day, curing them.
But that is not the point of the trial at this time. At this point the goal is still to establish that injecting stem cells is safe for the patient, won't cause more damage to the patient, and won't lead to the patient reject the cells. Early data from the first 12 patients, who had injections in the lower back, shows this procedure is safe.
Injecting anything into the spinal cord is very dangerous because it can cause serious damage. To avoid injuring the spinal cord, which is always moving as the patient breathes, the needle delivering the stem cells has to move along with the body.
Boulis invented an apparatus that resembles a miniature oil rig mounted on to the patient's spine. It moves with every breath and holds a super-fine needle through which to inject the stem cells. To prepare for these surgeries, Boulis and his fellow surgeons practiced mounting the apparatus on pigs, which are close in size to humans.
The first 12 patients in this clinical trial had the "rig" mounted on their lower back, giving surgeons a flatter surface to work with.
But the injection site on Grosjean is on the neck, posing a new challenge for Boulis.
"It didn't fit exactly as I had envisioned it," he said immediately after the surgery. "In fact, I ended up applying it much in the same way that I had applied it in pigs, as opposed to how I had envisioned it in humans, and that gave us nice solid fixation."
Boulis screwed the structure to the spine on one side, but to the skull on the other side.
With the spinal cord exposed after removing part the spine and peeling back layers of muscle and membranes protecting the cord, the injections slowly began. They have to be slow -- injecting the cells too fast alone can damage the cord or the cells can spill out, never having a chance to nestle into the spinal cord.
After the third injection went smoothly, Boulis paused to note what they were accomplishing at this moment. After the surgery he said, "it is a big milestone for us. ... I think the biggest thing about this is that I feel like we finally arrived."
That's because Boulis and his colleagues have come a long way, through trial design; to testing the cells in mice to ensure they don't cause tumors, which sometimes happens with stem cells; to inventing the needle-holding oil-rig-like apparatus; to practicing on many pigs; to perfecting how attach the device to patients.
"Finally we're beginning to inject cells into the segments that control the diaphragm, and to the extent that we are able to do that safely ... this is where we keep people breathing," Boulis said.
And that's ultimately what this clinical trial is about.
Glass described Friday's surgery as being at the beginning of crossing an important threshold. "I think it's a huge step forward. I don't want anyone to think that we have a cure for this disease. We don't. But we now have a whole other way to approach it, and that's really what's exciting and important."
Feldman described the day as the most momentous in their pursuit of using stem cells in the treatment of ALS.
"I have spent over 25 years taking care of patients with ALS, and I feel today I can go back to them and give them hope," she said.
Alan Trounson, president of the California Institute for Regenerative Medicine in San Francisco, agrees, calling the progress in this clinical trial a "big step forward."
Every clinical trial that can show a stem cell procedure to be safe is important, he said.
"These are tough diseases," Trounson said. He agreed that being able to safely inject stem cells into the cervical area of the spinal cord is an important step forward for patients with ALS and potentially other neurodegenerative diseases such as multiple sclerosis.
Grosjean, Glass and Boulis are quick to point out that they have to replicate this surgery in other patients. Two more patients will receive the same cell dosages in the near future in this part of the clinical trial.
After telling Tracie Grosjean how well the surgery went, Glass was excited and cautiously optimistic.
"We're moving forward," he said. "We don't have a treatment yet, we don't have cure yet and there's no evidence yet even putting these stem cells on the spinal cord is going to either slow the disease or prevent progression or even make it better."
Three days after the surgery, Boulis said the patient was doing well. Neurologically he is where he was before the surgery. His legs and arms are moving, confirming what was monitored throughout the entire surgery. The spinal cord was not damaged.
Tracie Grosjean said her husband is still in pain, which doctors say is expected given the surgery. But she said the doctors tell them he's doing great and they hope be home in time for Thanksgiving.
After Geron, Stem Cells’ New Saviors
When the biotech company Geron announced this week that it was halting its pioneering stem-cell program—whose centerpiece is a clinical trial in which four paralyzed patients with spinal-cord injuries were injected with cells derived from embryonic stem cells...
the chief scientist at a rival firm had one thought: “I guess that leaves us holding the flag,” Robert Lanza of Advanced Cell Technology told me. “There’s a lot of weight on us to deliver now.”
The Geron study was famous for being the first to treat patients with cells taken from human embryos, and its premature end, due to financial concerns, may seem like a disappointing finale. Fortunately, at least two lesser-known firms are swooping in to continue similar groundbreaking research—perhaps with even more promise and practical applications—and with the potential to revolutionize medicine. One is forging ahead with an extraordinary new test today.
The better known of the two, ACT, has the only other Food and Drug Administration–approved clinical trials using embryonic stem cells, as Newsweek recently described: one trial is for patients with Stargardt’s macular dystrophy and one is for age-related macular degeneration. Both diseases cause blindness. (The studies are notable because Catholic nuns are among the patients, even though the Vatican has condemned stem-cell research.)
But there’s also Neuralstem Inc., which is in the midst of a clinical trial for ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease). Today, if all goes as planned, the first ALS patient will receive an injection of stem cells into the upper part of his spine—the first step toward determining whether the experimental therapy can save ALS patients from dying when their motor neurons, which control muscles, become too weak to maintain breathing.
In ALS, motor neurons in the spinal cord and brain deteriorate to the point where, eventually, they can no longer signal muscles to move. As a result, patients become paralyzed and, when motor neurons controlling respiration die, unable to breathe; most die within three to five years of diagnosis, and only one quarter survive at least five years. There’s currently neither a treatment nor a cure for ALS.
Neuralstem, based in Rockville, Md., uses cells slightly older than the days-old embryonic stem cells Geron used, opting for “neural” stem cells. Unlike embryonic stem cells, which can differentiate into the 200-plus kinds of human cells, neural stem cells have already chosen their fate; they can become any of three kinds of cells in the central nervous system (neurons, astrocytes, or oligodendrocytes). Neuralstem obtained all the cells it has needed so far from an eight-week old fetus that was aborted in 2000.
The procedure has been attempted on 12 ALS patients so far, starting in January 2010. They received either five or 10 injections of 500,000 or 1 million neural stem cells, respectively, into the lower (lumbar) region of the spine, in a procedure developed and performed by neurosurgeon Nicholas Boulis of Emory University, under the direction of Emory neurologist Jonathan Glass. The patient lies on his belly, and Boulis makes an incision and removes two layers of bone covering the cable of nerves that is the spinal cord. Then, guided by an MRI that shows where the motor neurons are, Boulis injects the stem cells, which takes about two minutes.
Although the goal of this early trial is to determine whether the procedure is safe—which it seems to be, although two patients have since died of ALS—the scientists have also seen hints that the cells benefit the patients. Ted Harada, 39, was a manager at Shred-It, a mobile shredding service based near Atlanta, when he was diagnosed with ALS in 2010, and by the time he enrolled in the study he was able to walk only with the help of a cane. Climbing stairs was difficult, he recalls, and he was easily fatigued and often out of breath. He was unable to raise his left leg while sitting if someone pressed on it even lightly, and his left arm was also losing strength.
Since receiving 10 stem-cell injections last March, Harada has improved enough to complete Atlanta’s two-and-a-half mile Walk to Defeat ALS on Oct. 22. “I still have ALS, but I’m starting to see signs of hope,” said Harada.
Studies of lab animals suggest how the neural stem cells might be benefiting Harada and other patients. The cells remain where they are injected in the spine, says Karl Johe, chief scientific officer of Neuralstem, right beside a high concentration of the motor neurons that are being killed by ALS. There, although the stem cells cannot resurrect dead motor neurons, they can keep additional ones from dying, explains Johe: they produce protective molecules.
Protecting neurons only keep ALS from getting worse, however—they don’t reverse it. One reason Harada regained movement and strength might have been that the injected stem cells also cause axons—the long tails on neurons that connect neuron to neuron as well as to muscle—to regrow. “The connection that the motor neuron makes to the muscle is the first thing that goes in ALS,” explained Glass, possibly because the neuron becomes too weak to support the long axon that connects to the muscle. “It might be that if you can rescue the cell body [with neural stem cells], you can rescue that connection,” said Glass.
Animal studies suggested just that, said Eva Feldman, director of the A. Alfred Taubman Medical Research Institute at the University of Michigan and an unpaid adviser to Neuralstem: “You can hypothesize that if the nerve cell is just about to give up the ghost, the stem cells preserve it and the axonal connection is restored, with the result that the patient has a restoration of function.”
Today, for the first time, Boulis is scheduled to inject neural stem cells not into the lower part of patient’s the spinal cord, to restore movement in the legs, but into the upper region, to target motor neurons that control respiration.
Neuralstem believes that neural stem cells could also treat spinal-cord injury—the condition Geron targeted—and Huntington’s disease, in which neurons in the brain are killed much as they are in ALS. The company has requested FDA permission to launch a spinal-cord injury trial.
ACT, too, “remains committed to embryonic stem2cell research,” said Lanza. “We have no intention of letting [Geron’s decision] interfere with our mission.” The company’s clinical trial, at UCLA, uses what are called retinal pigment epithelial cells, grown from embryonic stem cells, to treat two causes of blindness, Stargardt’s disease and macular degeneration. (Stem cells from a human embryo are grown in the lab, and after they differentiate into the kind of cell needed for the disease being targeted, they’re injected into patients.) “We’re moving full steam ahead,” said Lanza, making final arrangements for other sites to enroll patients. Although results have not been formally reported yet, the first patients—who received stem cell–derived treatment this summer—are doing well enough, Lanza said, that “both want us to treat their other eye.”
In contrast, it would have taken years for Geron to see whether the cells it had derived from embryonic stem cells helped spinal-cord patients regain movement. “Many of us were surprised Geron selected spinal-cord injury in the first place,” said Lanza. “It didn’t really make a lot of sense, either commercially or biologically. So it’s not too surprising they didn’t obtain any biological effect. Although treating spinal-cord injury has a kind of sex appeal, you have to take reality into account, including not only the market but the chances of success.”
Could This Be the End of Embryonic Stem Cell Research?
A biotech company that after much turmoil and huge expense launched the first human embryonic stem cell clinical trial in the United States is getting out of the stem cell business.
Geron led the charge to push the U.S. government and society at large to allow use of embryonic stem cells. Scientists believed they could treat myriad diseases because of their ability to become any cell in the human body. But the company has accumulated losses of almost $300 million over the past four years and has halted its stem cell efforts. With few scientists pursuing stem cell research of the embryonic variety, many are wondering if commercial embryonic stem cell research will soon take its final breath.
The cells are controversial because human embryos are destroyed to obtain them. But the company persevered amidst years of public outcry and political punditry and in October 2011 launched the first-ever FDA-approved human trial to treat acute spinal cord injuries. Just four of the 10 approved patients have been treated with Geron's cells, and now it looks like the other six won't have their chance. A recently-launched Swiss trial run by Geron will also presumably be halted. The company has laid off 34 percent of its staff and will focus now on cancer treatments. Many patients who held out hope for a paralysis cure will be sorely disappointed.
Advanced Cell Technology is one of the only companies (Stem Cells is another) still using embryonic stem cells. It has human clinical trials active in macular dystrophy and macular degeneration.
But other companies, like Neuralstem, are poised to pick up the slack using a different and less controversial type of stem cell. Neuralstem uses neural rather than embryonic stem cells, and has already seen remarkable success treating ALS (AKA Lou Gehrig's disease) patients, which I wrote about here. Neural stem cells are not completely free of controversy: they are taken from a voluntarily aborted fetus. But embryos are not destroyed in order to obtain them. And Neuralstem's technology allows them to proliferate all the cells they need from a single fetus.
"This was not a surprise to me," Richard Garr, CEO of Neuralstem, said about the Geron news. "I think the writing was on the wall when Tom Okarma was either pushed out or left on his own. It was pretty clear the they were not interested in being a stem cell company at that point."
Okarma was Gerons's CEO for 13 years and was the public face of the company's fight to use embryonic stem cells.
Meanwhile, Neuralstem has already treated 12 ALS patients, and doctors will treat number 13 on Friday. Garr believes his cells are easier to control and target than embryonic stem cells for treating neural diseases.
Next up for Neuralstem is a human trial testing their cells in chronic spinal cord patients. So we might be saying goodbye to Geron, but not to the hope of spinal cord injured folks getting out of their wheelchairs.
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