ALS Stem Cell Therapy Shows Safety and Efficacy in Early Clinical Trials
Neuralstem reports NSI-566 slowed disease progression and improved muscle and lung strength
January 29, 2016
By Magdalena Kegel
Biopharmaceutical company Neuralstem presented new and potentially promising results from its clinical investigations of NSI-566 — human spinal cord-derived neural stem cells for the treatment of conditions including amyotrophic lateral sclerosis (ALS) — at the recent Phacilitate Cell & Gene Therapy World conference in Washington, D.C.
Mostly, the problem is due to improper blood cialis without prescription circulation and ways to enlarge penis can be used to deal with impotency and Ed. Canadian Neighbor Pharmacy decides to explain men how levitra vs viagra may help cope with erectile dysfunction (ED). Whether it is reducing general weakness, improving energy levels, performance and endurance: When it comes to natural methods to increase stamina, the following benefits can be enjoyed by users of these capsules: Aging and low immunity Fatigue and weakness Poor stamina and low energy Weak erection and erectile dysfunction in men. prescription viagra without The mighty Himalayas have many secrets that many people at the lower altitudes sildenafil price in india of Earth still don’t know. Karl Johe, the company’s chairman and chief scientific officer, reported that two clinical trials of NSI-566 in a total of 30 ALS patients have been completed and met safety endpoints. NSI-566 is also currently in a Phase 1 trial for treating paralysis due to chronic spinal cord injury, as well as in a Phase 1 trial to treat paralysis from ischemic stroke
The presentation emphasized the treatment’s consistently demonstrated biological activity and several modes of beneficial actions, such as motor neuron rescue, motor improvement, and neuronal integration of the stem cells. The data presented originated from both human and animal studies.
To date, NSI-566 cells have been administered to 40 patients across four investigational safety trials. The dosing ranges are between 1.2 million to 24 million cells per patient, and the treatment has shown a high safety profile, with both Neuralstem and collaborators at research institutions stating that data support the treatment’s further clinical development in all three indications.
“The consistent biological activity of motor improvement by NSI-566 across multiple disease conditions in humans supports our regenerative hypothesis and is consistent with our preclinical data,” Dr. Johe said in a press release. “Based on these encouraging results, we are preparing to conduct additional clinical trials in each of these incurable neurodegenerative indications.”
Data from both the Phase 1 and Phase 2 ALS trials showed that patients improved on multiple levels, including better lung capacity and muscle strength, and experienced slower ALS progression. Phase 2 results also revealed that more than half of the patients had a reduction in the ALS Functional Rating Scale (ALSFRS) decline compared to historical data. The remaining patients — most exhibiting very low grip strength at the study’s start — did not experience a change in their rate of decline.
Neuralstem said that it intends to limit the next ALS trial of NSI-566 to patients with enough muscle strength to potentially benefit from the therapy.
Scientists Seek Stem Cell Cure For Spinal Cord Injuries
By: Emily Berman // January 25, 2013
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Thomas Hazel, Ph.D, and Richard Garr pose in their neural stem cell laboratory, in Rockville, Md.
Neuralstem, a Rockville-based biotech company, has just been approved by the FDA to begin implanting stem cells into people with spinal cord injuries. While there’s a long scientific journey ahead, this trial could mean hope for paraplegic and quadriplegic patients all over the world.
The nervous system works, by sending electrical signals up and down the spinal cord. Degenerative diseases like Multiple Sclerosis, ALS, or Parkinsons impair the ability to send those signals. “There’s a gap,” says Richard Garr, co-founder and CEO of Neuralstem. He says there’s something that’s blocking signals from getting through.
Unlike our skin cells, the central nervous system doesn’t repair itself when damaged. “You’re born with a certain number of neurons, and that’s the way it is.” says Garr.
In 1998, Garr met Karl Johe, Ph.D. who had made a discovery while working at NIH. Around week 7 or 8, when the human embryo is the size of the tip of your thumb, there are cells in the brain area of the embryo that have all the information they need to become neurons. These are called ‘neural stem cells.’ Dr. Johe developed and patented techniques for extracting and multiplying these cells, then implanting them as ‘replacement neurons.’
“We’re actually putting in cells that are going to turn into neurons that are going to bridge the gap,” he says. “We’re creating new circuitry.”
Dr. Thomas Hazel, the head of Research at Neuralstem, explains one of the most important aspects of neural stem cells is that they can easily replicate. The lab received a donated tissue from a legally aborted fetus about 10 years ago, and they’ve been using those cells ever since.
The surgery recently approved by the FDA is much like an earlier trial, done on ALS patients. The surgeon injects neural stem cells directly into the patient’s spinal cord. Those stem cells grow into neurons, and if all goes according to plan, they help messages pass from the brain to muscles.
The ALS trial is waiting for phase 2 approval, but patients, on their own, are reporting some improvement. The spinal cord trial will take on eight patients who have experienced injury in the past 1 to 2 years in the thoracic spine, which is from the chest, down. Neuralstem will announce the partner hospitals in the coming months, and hope to start the surgeries in summer 2013.
The biotech Geron may have abandoned its famous effort to treat paralyzed patients with stem cells—but two rivals are swooping in to do groundbreaking trials, Sharon Begley reports. So far, their results are even more promising.
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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.
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 keeps 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 his patient’s 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.
‘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.’
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.”
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(CNN) — A little more than two years ago, Ted Harada felt his left leg weakening, and he found himself quickly running out of breath. Doctors first thought he had asthma, but in May 2010 they told him he probably had ALS, or Lou Gehrig’s disease.
In August 2010, doctors confirmed Harada, then 38, had the fatal disease, and he knew it was progressing.
“Every month they [doctors] could see deterioration,” Harada said.
ALS patients lose muscle function in the lungs until they can no longer breathe. Most people with ALS die from respiratory failure within three to five years of first symptoms, according to the National Institute of Health. The disease causes nerves to wither and the lungs to stop working. About 10% of ALS patients live 10 years or longer.
Harada joined a clinical trial at Emory University in Atlanta, where doctors were injecting neural stem cells — the precursors to nerve cells — into the lower spinal cord of ALS patients.
Before the procedure, Harada walked with a cane and would get winded just by walking to the mailbox. He had to quit his job as a manager for a shredding company. He was so tired he couldn’t play with his three children. He was too weak to pick up his youngest child. He couldn’t even open a Ziploc bag.
Harada hoped the treatment would help, but he didn’t expect it to. However, two weeks after getting the stem cell injections in March, he says he started to feel better.
“It’s been nothing short of miraculous,” he says. “I cannot begin to explain the difference it has made.”
He hasn’t touched his cane in months, he says, and his breathing has improved.
“I was afraid I would wake up and the improvements would be gone,” Harada said.
Dr. Jonathan Glass, who is overseeing the clinical trial at Emory, and Dr. Nicholas Boulis, who invented the surgical procedure used to inject the stem cells, explained to patients that participation in the trial would not cure or even benefit them personally, but it would help doctors learn more about how to treat ALS in the future.
The first phase of any clinical trial is to prove that a treatment won’t injure patients, not that the treatment works, said Dr. Eva Feldman, who designed the clinical trial at Emory.
The first part of the ALS study, sponsored by the Maryland-based biotech company Neuralstem, is designed to show that the surgical procedure to inject the stem cells into the spine is safe, and that the patients’ bodies won’t reject them. According to researchers, the cells did not harm any of the 12 patients in the Emory study, nor did they accelerate the progression of their ALS.
“I need to temper my excitement because it’s a very small patient population,” said Feldman, president of the American Neurological Association. But the facts are not discouraging. She presented early data from the study Monday at the neurological group’s annual meeting in San Diego.
“We have cautious optimism that a few of the patients may have slowed in their progression of lower extremity weakness, and one patient may have improved,” her report said.
Of the 12 patients in the trial, two have died.
John Cornick’s disease had progressed further than Harada’s by the time he received the stem cell injections in 2010. He was already in a wheelchair, and he knew participating in the clinical trial wouldn’t cure him. But he told CNN in April 2010 that the only way doctors were going to figure out how to cure ALS was to have people willing to participate in clinical trials.
“For me it just seemed like the right thing to do,” he said.
Cornick died of ALS in May. Another patient in the study, a 39-year old man, died of a heart attack.
Feldman said the conditions of eight of the remaining 10 patients have not changed. Based on these results, she and her team in Georgia are asking the Food and Drug Administration to allow them to move to the next part of the trial: Injecting stem cells higher on the spine – into the cervical spinal cord, which is in the neck.
Harada is optimistic that research like this will give other patients hope and lead to treatments in the future. He realizes he hasn’t been cured, but it’s like his clock has been set back, he says. He feels like he did when symptoms first started to appear in 2009.
“I know I still have ALS. I am so grateful for this gift regardless of how long or short it lasts,” he said.
“I can go through most days without thinking I have ALS.”
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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.”
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CNN’s Dr. Sanjay Gupta reports on a new stem cell clinical trial that is making history.
http://alsnewstoday.com/2016/01/29/clinical-data-from-nsi-566-als-trials-presented-by-neuralstem/
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.
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