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.
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.”
http://alsnewstoday.com/2016/01/29/clinical-data-from-nsi-566-als-trials-presented-by-neuralstem/