ALS Stem Cell Therapy Shows Safety and Efficacy in Early Clinical Trials

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

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.

Planned Parenthood Video: Why Use Tissue From Aborted Fetuses?

http://www.nbcnews.com/health/health-news/planned-parenthood-video-raises-question-why-use-tissue-fetuses-n393431

Activists who released a video they say shows a Planned Parenthood doctor discussing the sale of tissue from aborted fetuses have riled up abortion rights opponents, with House Speaker John Boehner saying the case makes him want to “vomit” and Republican controlled committees in Congress promising to investigate.

Amongst the entire prescription free viagra leading pill is said to be Kamagra online. best online viagra Remember, these medicines work only in the presence of the right amount of minerals and vitamins. It’s a treat for the fans of Hip-Hop. “Celebration” byKool &The Gang The song was viagra pills part of the 2010 movie Eat Pray Love. The effectiveness of the medicine is purchase generic viagra however not questioned as it has shown possible results for men of all ages. The political firestorm raises a question: Why would anyone use tissue from an aborted fetus? It’s because some scientists hope they might provide cures for a range of diseases from Parkinson’s to crushed spinal cords.

Click here to read the full article…

UM researcher uses stem cells to fight Alzheimer’s

The Detroit News

UM researcher uses stem cells to fight Alzheimer’s

http://www.detroitnews.com/story/news/local/michigan/2014/11/11/um-researcher-uses-stem-cells-fight-alzheimers/18895621/

Kim Kozlowski, The Detroit News 11:38 p.m. EST November 11, 2014

Ann Arbor — Inside a laboratory at the University of Michigan, researchers have been injecting stem cells into the brains of mice engineered to have Alzheimer’s disease, and making remarkable discoveries.

The experiments are among the first in the nation to examine how stem cell therapies might alter the course of Alzeheimer’s, a fatal disease that afflicts more than 5 million people in the U.S. and is widely regarded as an epidemic predicted to explode as the nation’s population ages.

The research is being overseen by UM’s Dr. Eva Feldman, who pioneered the nation’s first clinical trial using stem cells in patients with amyotrophic lateral sclerosis — a disease that received global awareness last summer thanks to the ALS ice bucket challenge.

Dr. Feldman

While Feldman’s ALS trial is not complete, it is showing promise. That’s why she began an experiment to see how stem cells might fare in treating Alzheimer’s disease, another neurodegenerative disorder.

Although it’s very early in the research, the Alzheimer’s experiment with mice showed that stem cells made a mouse with Alzheimer’s disease indistinguishable in behavior and memory from a mouse that didn’t have the disease.

“When you work in science, you do as many experiments that don’t work that do,” Feldman said. “When you get something that works so beautifully (like this experiment), you can quickly see its translational potential. I am looking at a mouse but some day I could be looking at a man. As a clinician scientist, those are the moments you live for.”

The findings from Feldman’s preclinical trial were presented last month in Boston at the Congress of Neurological Surgeons annual meeting.

While some experts are cautiously optimistic, others hailed Feldman’s work.

“The special design of the present study sets new standards for further clinical translation in regenerative medicine for neurological diseases,” Tamir Ben-Hur, a Jerusalem-based neurology professor, wrote earlier this year in the Annals of Neurology. “This study design represents the best moral solution for the difficult task of testing risky procedures in a deadly disease with no alternative therapy or hope.”

Feldman, a UM professor and neurologist, began testing stem cells years ago. Her research began with rats and pigs with ALS — also known as Lou Gehrig’s disease — before she launched a clinical trial in humans with the disease five years ago.

Last year, some participants in the human study either improved or stabilized in the closely watched clinical trial.

Soon after, the Alzheimer’s study was launched. That study used fetal stem cells provided by Neuralstem Inc., a Maryland company. It used mice that had been engineered with the inherited gene of Alzheimer’s but had not yet displayed symptoms.
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With one group of the mice, UM researchers injected the stem cells into the hippocampus, the area of the brain that controls learning and memory. Another group of mice were injected with saline solution. The mice that got the stem cells were evaluated with several behavioral and memory tests — and looked the same as mice without Alzheimer’s disease.

“Those animals retained their ability to think, as a mouse does, to recognize objects so they looked just like an animal that doesn’t have Alzheimer’s disease,” Feldman said. “It’s really remarkable.”

Feldman is still deciding which larger animal model to use for further research, but her associates say it likely will be rhesus monkeys.

“She’s doing stuff that needs to be done,” said Robert Karbel, manager of the Sinai Medical Staff Foundation in Southfield, a group of physicians that has supported Feldman’s research with $500,000. “She has the courage to do it … and she seems to be making progress. There are no cures yet, but she’s working at it.”

Feldman’s latest study is generating excitement because if successful, it has the potential to impact millions of lives. About 5,600 people are diagnosed with the disease each year, according to the ALS Association, but Alzheimer’s afflicts 100 times more people, not counting their family caregivers.

Alzheimer’s is a fatal disease with no cure and no meaningful agents to delay its course. The disorder slowly robs people of their ability to remember and perform daily tasks, which is why so many end up in long-term care facilities.

As the baby boomer population ages, many regard Alzheimer’s as a tsunami that could swamp the nation’s health care system if a better intervention is not discovered, in part because of how costly it is to care for its victims.

In 2014, the direct costs to care for those with Alzheimer’s will total an estimated $214 billion, including $150 billion in Medicare and Medicaid costs, according to the Alzheimer’s Association.

By 2050, those costs are expected to soar to an estimated $1.2 trillion.

There are all kinds of studies — nearly 50 — in various stages of research to address the disease. But Feldman is among the first to examine stem cells, according to Dr. Keith Fargo, director of scientific programs and outreach at the Alzheimer’s Association.

Fargo said the research is very preliminary, and should be regarded cautiously. But he also said it is intriguing.

“We think all kind of research is needed,” Fargo said. “We support a full-court press in Alzheimer’s disease research.”

For people like Ted Harada, the research is more personal. Harada, 42, of McDonough, Ga., was in the first phase of Feldman’s ALS trials, shortly after he was diagnosed with ALS in 2011.

He received millions of stem cells in his spinal cord in two separate surgeries.

By his doctor’s predictions, he could have already lost his battle to the disease. Instead, he no longer uses a cane and has stabilized.

“We’ve all heard for years that stem cells could be the next big frontier in medicine,” Harada said.

“It’s great they are finally allowing these type of trials and I am so thankful researchers like Dr. Feldman are on the front lines pushing the envelopes and not accepting the status quo. Her research is giving hope to communities where hope was an absent commodity.”

 

Spinal gap: Neuralstem goes into chronic injuries phase I trial first ever to be cleared by the FDA

click here to read the full article

By Randy Osborne, Staff Writer
With encouraging data from a phase I trial in amyotrophic lateral
sclerosis (ALS) and a phase II trial under way testing NSI-566,
Neuralstem Inc. has begun – with the same candidate – the fi rst
human neural stem cell study to be given the FDA’s nod for chronic
spinal cord injury.
Four patients with thoracic spinal cord injuries (T2-T12) will
have NSI-566 transplanted directly into the region of the injury,
which has been sustained between one and two years before the
treatment. All patients have an American Spinal Injury Association
grade A level of impairment, which means complete paralysis with
no motor or sensory function at and below the trauma site.
Richard Garr, CEO of Germantown, Md.-based Neuralstem, said
the trial is half the size originally planned, and for a good reason.
“When we submitted this originally, there were eight patients, but
that was before we had treated successfully the high-dose patients
in our ALS trial,” he told BioWorld Today. “We went back to the FDA
and asked them to amend the protocol.”
Last heard from in the stem cell/spinal cord injury space was
Menlo Park, Calif.-based Geron Corp., which last year disclosed in
an SEC fi ling that the assets related to the program were taken
over by Asterias Biotherapeutics Inc., a subsidiary of regenerative
medicine specialist Biotime Inc., of Alameda, Calif.
The deal involved transfers of common stock and warrants, along
with patents, regulatory fi lings and investigational new drug
applications fi led with the FDA for Geron’s phase I safety study
with the oligodendrocyte progenitor cells (OPCs). Geron was
investigating the cells’ effi cacy in acute spinal cord injury, rather
than chronic, as with the Neuralstem product. In May of this
year, Asterias offered promising safety results with AST-OPC1, a
population of cells derived from human embryonic stem cells
that contain the OPCs, in fi ve subjects tested during a restarted
experiment that Geron began in 2010. (See BioWorld Today, Jan.
26, 2009, Jan. 27, 2009, and April 5, 2013.)
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FDA won’t just let you go in to try. The surgery is very risky. We’re
the first ones who ever did intraspinal injections with our ALS trial.”

Neuralstem had to use a special delivery device invented
at Cleveland Clinic, and deliver strong preclinical data
to U.S. regulators before efforts could move ahead. The
fi rm’s approach is “very different from what anybody else,
even Geron, has ever done,” he said.
Predicting how fast benefi t might appear is tricky. “In ALS
patients, the maximum window of biological activity for
the cells was between four and six months post-surgery,”
Garr said. “But it was also very clear in four to eight weeks
that there was considerable biological functional activity.
Will we see that in spinal cord patients? We don’t know,
but that would be our expectation.”
For some ALS patients, the effects turned up much sooner,
he added. “What the cells are doing here, in chronic
[spinal cord injury] patients, is literally bridging the gap.
We’re trying to rebuild the circuitry in the gap so that the
signal can come through, down the spinal cord. There are
also a lot of neurotrophic factors expressed by the cells
that can help with healing, but in a chronic patient, it’s
unknown how much impact that will have.”
Garr cited a key difference between spinal cord injury and
ALS, “where you are putting the cells in the motor neuron
pools to protect and nurture the remaining motor neurons
and then hopefully nurture back to health those that
haven’t hit that tipping point. The early neurotropic factor
expression of the cells, even before they are synaptically
integrated and matured, could have an effect [in ALS] –
clearly has. Maybe in spinal cord injury patients, where the
neurotrophic effect isn’t the primary reason for benefi t,
it could take a little longer. We’re really waiting for the
synaptic connections to happen and for the circuitry to be
rebuilt.”

 

Online Chatter Could Unravel Carefully Built Construct of ‘Blind’ Clinical Trials

Researchers Fret as Social Media Lift Veil on Drug Trials

Online Chatter Could Unravel Carefully Built Construct of ‘Blind’ Clinical Trials

http://online.wsj.com/articles/researchers-fret-as-social-media-lift-veil-on-drug-trials-1406687404?mod=WSJ_hp_RightTopStories

By

Amy Dockser Marcus

July 29, 2014 10:30 p.m. ET

 

On her first day in a clinical trial for an experimental multiple sclerosis drug, Jeri Burtchell was convinced she was getting the new drug, not the standard therapy that some patients were randomly assigned to receive.

When she bumped into the trial’s lead investigator in the elevator that day, she told him, “I think I know which drug I’m on!” The doctor put up his hands, waving her off. “Don’t tell me!” Ms. Burtchell recalls him blurting. “I can’t know!”

A nurse later explained to her that knowing who was getting what could compromise the research. Even so, Ms. Burtchell went home and recounted the incident to followers of a blog she was writing about the trial. “The mystery medicine is doing its job,” she wrote.

For decades, the clinical trials vital to developing new drugs have followed a central principle: Researchers and patients must both be “blinded” as to who is getting the experimental drug and who a placebo or standard therapy.

If patients know who has the new drug, or learn too much about how others in the trial are faring, this knowledge could influence how they report symptoms and make it hard to tell whether the drug is working. Staying in the dark throughout a trial is a standard held sacrosanct by researchers. But lately, not so much by patients.

On Facebook groups, online forums and blogs, some patients are effectively jeopardizing the blind. In trials for hepatitis C, multiple sclerosis and ALS (Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease), patients have been sharing details of their reactions and trying to figure out whether they are getting the active drug.

Patients also swap tips on how to get accepted into trials, even if they don’t meet all the requirements. Some who are in trials collect and analyze their medical data and others’ to get an early indication of whether a drug will be a success.

Drug makers and researchers are increasingly concerned that online chatter could unravel the carefully built construct of the clinical trial, and perhaps put patients in danger. They worry that patients may drop out if they suspect they aren’t getting the drug being tested, or may report symptoms inaccurately because of the influence or suggestions of others in the trial.

Patients who share too much “could effectively chill a new drug before it ever gets to patients by misinterpreting early signals,” says Craig H. Lipset, head of clinical innovation at Pfizer Inc., who wrote an opinion piece in Nature Medicine in March calling on trial sponsors and regulators to study the effects of social media. “It’s scary.”

Patients, for their part, often say they have the right to talk about their experiences. In life-threatening diseases such as ALS, patients “want, need and deserve to know” how others are doing, says April Moundzouris, a Chattanooga, Tenn., woman whose “April’s ALS Blog” chronicles her experience with an experimental stem-cell treatment. The early-stage research by Neuralstem Inc. isn’t blinded.

Neuralstem Chief Executive I. Richard Garr , a close reader of April’s blog and those of other patients, says the sharing may pose a challenge later on when it comes time for a trial designed to prove efficacy to the Food and Drug Administration. That trial would likely have to be blinded.

A patient who blogs that he or she isn’t feeling well, isn’t improving or has some symptom can sway how other patients report or their willingness to join a trial, Mr. Garr says.

This is just one of the ways the Internet and social media bear on the drug-discovery process. Richard Bedlack, who runs the ALS clinic at Duke University, is involved in a project that asks patients to tweet tips about alternative and off-label treatments that he and other doctors assess to see if they might make promising research candidates.

By contrast, some pharmaceutical companies have tried to avoid using social media so they won’t learn about something that might make clinical analysis of an experiment more challenging or might have to be reported to FDA, according to Joseph Kim, an executive at Irish drug maker Shire PLC.

Says Mr. Garr: “The FDA is going to have to figure out how to accommodate social media.”

A spokeswoman for the FDA says the agency doesn’t have a policy on subjects in trials using social media to communicate with one another.

PatientsLikeMe, a Cambridge, Mass., company that runs a patient network and research platform where patients share health information, including during clinical trials, is wrestling with how to address the effects the constant sharing of information can have on trials.

In a 2012 paper, Paul Wicks of PatientsLikeMe wrote that according to the company’s data, a little more than 400 patients on the site have added treatment information that shows they are on a clinical trial. If patients start trying to determine if they are receiving the new drug, he asked, “how should we respond to this as researchers or as a company?” Dr. Wicks says the company is trying to get patients and researchers to work together to design trials, believing that collaboration will lead to better understanding of the issues.

To date, no clinical trial has been stopped because of online sharing of patients’ experiences. But drug makers are starting to take pre-emptive steps.

Shire helped create educational videos about the consequences of sharing too much, working with a Boston-based nonprofit called the Center for Information and Study on Clinical Research Participation. In one animated video, a blue bean’s description of side effects from a drug causes a yellow bean to drop out of a study. Shire, whose board has agreed to a takeover by AbbVie Inc., tells patients how to download the videos.

“The industry needs to do a lot more,” says Shire’s Mr. Kim, director of patient recruitment and engagement. “It is a hard thing to modify behavior without it being too controlling.”

Vertex Pharmaceuticals Inc. was testing a drug for hepatitis C when Lindsay McNair, then its senior medical director, got an alert from an investigator that patients in the trial were posting about it. She went to MedHelp.org, a site that hosts patient message boards, and started reading. “They were really incredible threads,” she says.

generic viagra prices Also keep a good check on the storage as well. It has some outstanding features can enhance your sexual desire and improve sexual function. http://davidfraymusic.com/events/theatre-croisette-cannes/ buying viagra in india If you want to purchase the medicine of viagra no prescription overnight , you have to log in to the particular site and make an order for that. The viagra uk sales effects of testosterone injections are not rapid. One patient advised those who wanted to know whether they were getting the experimental drug to ask a doctor not involved in the trial for a test of viral load. If it had dropped dramatically, the patient wrote, that was a sign the person was getting the new drug, because standard therapy wouldn’t have such an effect. Some patients discussed dropping out if they concluded they weren’t getting the new drug. (Some did quit the trial, though it isn’t known if online sharing was a factor.)

Dr. McNair discussed the posts with others at the Boston-based company. They were concerned about patients harming their health by not reporting symptoms out of concern they could be taken off the trial. If enough dropped out, it might be hard to get an adequate test of the drug, says Dr. McNair, now chief clinical research officer at WIRB-Copernicus Group, which provides regulatory and ethical reviews of research.

So for its next trial, Vertex added an unusual paragraph to the consent document for subjects, explaining that rumors about side effects or about the drug’s efficacy might affect results and require doing the study over. Participants should feel free to discuss their participation with family, friends and medical providers, the paragraph said, but not publicly such as in Internet message boards.

“It was meant to be informational and educate about the implications discussions could have, but not to say they can’t talk or there would be repercussions if they did,” says Dr. McNair.

Not all the patients understood this. One who signed the document then posted on the MedHelp Hepatitis C forum: “There’s no specific legal recourse spelled out, but there is another section that states that my participation in the study can be ended at any time without my permission.” The patient wrote that the forum provided him with important information about managing his disease and about the trial. “I hope people will still talk to me here?!” he added.

Vertex says oversharing on social media isn’t grounds for eviction from a study. It continues to warn about the problem in consent forms. Vertex says there was no effort to identify or remove from the trial the person who posted on the MedHelp forum.

The hepatitis C drug won FDA approval, and now is sold as Incivek, but “the experience was nerve-racking,” Dr. McNair says.

Dr. Bedlack of Duke says the information patients share online can turn out to be incorrect. Before revealing the drug information at the conclusion of a trial, he often asks patients to guess whether they got active drug. “Most times they don’t get it right,” he says.

Ms. Burtchell, the multiple sclerosis patient, did guess right.

Now a 53-year-old resident of East Palatka, Fla., she was diagnosed in 1999 with the kind of MS that involves relapses interspersed with remission. By 2007 she estimates she had suffered nearly 30 relapses and was so exhausted she had difficulty caring for her young son.

She enrolled in a trial for an experimental therapy from Novartis AG that aimed to be the first pill for the disease, which was treatable only with injectable drugs. The trial matched one of injectable therapy, Avonex, against the experimental oral drug, called fingolimod.

Ms. Burtchell started a blog to chronicle her experience from start to finish. In the post after her first treatment, she told why she believed she was getting fingolimod.

In the past, she had taken injections for her condition. In the trial, she didn’t feel the stinging or pain she remembered from shots—a sign, she believed, that her injection in the trial was a placebo.

Also, after she was given a pill, she noticed a nurse recorded a fall in her blood pressure, which she knew was a potential side effect of the experimental drug.

Nearly three months into the trial, Ms. Burtchell posted that, for the first time since her MS diagnosis, she was able to hop on one foot.

“Maybe it’s the Fingolimod…,” she speculated. “Whatever it is, I feel better every day.”

When information on the study was revealed, it turned out she was indeed getting the experimental drug.

A spokesman for Novartis says consent forms for its trials don’t prohibit patients from talking about their trial participation. The spokesman says the company didn’t interact with Ms. Burtchell during the trial.

The drug was approved by the FDA in 2010 and now is sold as Gilenya. Novartis continued to study it in nonblinded research, in which Ms. Burtchell participated. Eventually, she served for a time as a paid speaker for Novartis, sharing her experiences.

She also continued to blog.

One of her followers was Pfizer’s Mr. Lipset, who was interested in how patients use social media.

In September 2011, he sent her a message on Twitter asking to talk. Mr. Lipset says he wanted to discuss the downsides of patients comparing notes. They talked, and each saw the other’s side.

Mr. Lipset says Ms. Burtchell helped him realize that “it’s not the patients who will change, but the researchers who have to change.” She reminded him, he says, that “ultimately patients are human beings. They are going to talk.”

In Ms. Burtchell’s post after their talk, she conceded that the Pfizer executive had made many good points. Even so, she concluded, “If I’m going to be poked and prodded, I’m going to be here blabbing about it.”

Later, her views started to shift. In 2012, Mr. Lipset invited her to appear on stage with him at a pharmaceutical-industry conference in Boston. She was asked if she ever worried about influencing others in a trial. “I think that is when the realization of what I had done really hit me,” she says.

At a February drug-industry conference in Miami where she was asked to speak about patients and social media, Ms. Burtchell proposed her own solution: that drug companies create online forums where patients can get practical questions answered by investigators and can commiserate with other patients about social issues in a moderated setting. She set up Partners in Research, a website that guides patients through the clinical-trials process.

She continues to take Gilenya for her MS and has had two relapses while on it, most recently in February. She is part of a study looking at its long-term effects.

But she has stopped her blog.

“I’m too aware of the impact,” she says, “too conscious of my audience, to blog like that again.”

New trial may be step forward for spinal cord injuries

http://thechart.blogs.cnn.com/2014/04/16/new-trial-may-be-step-forward-for-spinal-cord-injuries/?iref=allsearch

April 16th, 2014

Miriam Falco – CNN Medical Managing Editor

New trial may be step forward for spinal cord injuries

In what may be another step forward in treating spinal cord injuries, a safety trial will begin this year on the practice of injecting stem cells directly into the injury site, Neuralstem Inc. announced Wednesday.

The Maryland company said the University of California, San Diego’s Institutional Review Board had approved its clinical trial protocol, which also has approval from the Food and Drug Administration.

The first eight patients who will be enrolled will be paraplegics who had a thoracic spinal cord injury one to two years ago and have no motor or sensory function below the point of their spinal cord injury.

Thoracic spinal cord injuries are rare, according to the Christopher and Dana Reeve Foundation, because of the protection afforded by a person’s rib cage. In addition to the loss of function in legs, patients also experience a loss of physical sensation, bowel and bladder problems and sexual dysfunction. However, in most cases, function of the arms and hands are not affected.

It’s the latest trial designed to inject stem cells into patients’ spines. The trial is supposed to show that the drug – stem cells, in this case – is safe, although researchers hope to provide some benefit as well.

In 2009, California-based Geron Corp. not only injected the first stem cells into a patient’s spinal cord, it was the first to use the highly controversial derivative of human embryonic stem cells. But after treating at least four patients, the company chose to shut the trial down in 2011 because of its expense and the company’s focus on cancer research.
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One week later, Neuralstem began its clinical trial in patients with amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease. That trial used a new device to inject stem cells into the spine without causing additional injury to the spinal cord. Neuralstem’s cells are not embryonic stem cells but rather cells taken from fetal spinal cords, which have already started to become nerve cells.

New Jersey-based StemCells Inc. launched spinal cord trials in Switzerland in 2011, using its own type of neural stem cells also derived from fetal tissue. It injected its first North American patient in Canada this year.

Unlike the goal of the Geron trial (similar to StemCells’), which was to re-mylenate nerve cells to re-establish connections from the spine to the brain – like fixing an exposed wire by providing a new cover – the goal in this new trial is to “actually build new circuitry,” Neuralstem CEO Richard Garr said.

“The stem cells are injected directly into the area of the injury and jump the gap with the new circuitry we’ve built,” he said. “These cells don’t migrate to the site.”

In animal experiments, rats were injected with these human stem cells and recovered significant function in all lower extremity joints, according to Neuralstem. “The cells turned into neurons which grew a ‘remarkable’ number of axons that extended for ‘very long distances,’ bridging above and below the point of severance,” the company says in a statement, quoting study results from August 2012.

Neuralstem is trying to reconnect the nerve cells from below the injury site to cells above the point of injury to re-establish signals going to the brain, says Karl Johe, the company’s chairman and chief scientific officer, who developed the cells.

Johe says he hopes the first patient will have the surgery to get the stem cells by July. “And then it would occur about once a month,” he added.

As for the most recent research, which discussed a much simpler method called epidural stimulation, Johe says it’s a complimentary approach. This month, researchers showed that four patients who had had spinal cord injuries for more than two years were able to ‘reawaken’ their muscles, so to speak: move their legs when electrodes implanted in the back were turned on, providing electrical stimulation to the spinal cord.

“There has been debate whether the motor neuron circuitry is intact below the injury point,” Johe said. “So now we know for sure (it is).”

Stem cell trial seeks longer lives for victims of deadly ALS

 

Researchers at Emory University in the United States are hoping to extend the lives of patients diagnosed with the deadly neuro-degenerative disease, Amyotrophic lateral sclerosis (ALS). ALS kills by destroying a patient’s nervous system but in clinical trials, the scientists say injections of neural stem cells show promise in slowing the disease’s progress. Ben Gruber reports.
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Neuralstem’s $19.6M offering takes ALS bid through phase II

By Randy Osborne, Staff Writer
Neuralstem Inc.’s $19.65 million from a stock offering will help
advance the lead compound NSI-566 in amyotrophic lateral sclerosis
(ALS), which is “about halfway through” a Phase II trial, said CEO
Richard Garr.
Rockville, Md.-based Neuralstem is selling about 6.7 million shares
at $2.91 each in the offering. Each investor also gets a warrant to
buy half the number of shares purchased. Warrants bear an exercise
price of $3.64, and can be exercised for fi ve years.
Shares (NASDAQ:CUR) closed Friday at $2.97, down 19 cents.
Expected to close next week, the offering’s proceeds will get
Neuralstem through Phase II in the ALS effort with spinal cordderived
stem cells, as well as the small-molecule program, where
the company has “just completed a Phase Ib trial in major depressive
disorder,” Garr told BioWorld Today. “We’re looking at the data now,
and anticipate sometime in this quarter fi ling for a Phase II.”
Stem cell trials are neither much more expensive nor much cheaper
than tests of other therapies. “That’s always in the eye of the
beholder, isn’t it?” Garr noted. “Drug trials, especially for depression,
are expensive. Everybody knows what the FDA expects and what the
parameters are. It doesn’t cost us any more or any less than anybody
else.”
Cell therapy as a whole is “fairly expensive,” he said. “In terms of the
dollars per patient, it’s very expensive, but in terms of the numbers
of patients, because it’s fairly small, the overall cost is manageable.”
The Phase II trial in ALS got funding help from the National Institutes
of Health and from the ALS Association, he said.
“We have to wait six months after the last surgery for the trial to
end,” Garr said. “Sometime near the end of this calendar year, the
Phase II [in ALS] should be over completely.”
Neuralstem’s approach represents the world’s fi rst intraspinal
injections of stem cells. “This is a targeted surgery at various
segments of the spinal cord, and the cells actually go into the
motor neuron pools in those segments and synaptically integrate,”
Garr said. “There have been, in the past, people who have tried to
put what you would think of as adult stem cells – all kinds of bone
marrow and blood stem cells and things like that – into the spinalfl
uid cavity,” though such experiments took place “mostly in Mexico
and in Germany and other places,” as well as China, he said.
“Our approach is unique, actually rebuilding the circuitry,”
Garr said. “These cells don’t fl oat up and down in the spinal
fl uid, and they don’t migrate to the spinal cord. They’re going
in and creating new circuitry inside very specifi c segments
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groups of muscles, he noted. In ALS patients, when the
muscles that control breathing and swallowing give way, so
do the patients, not long afterward.
HUMAN DATA FUELING STOCK
Neuralstem also has been given clearance by the FDA to
start a spinal cord injury trial in complete paralysis patients,
using the same technology.
“Geron, of course, famously, had an approval from the FDA
[for trials] with their oligodendrocyte progenitor [GRNOPC-1]
cells to try to treat spinal cord injury,” Garr said. “I believe
they may have actually transplanted two or three patients
before they pulled the plug.”
Menlo Park, Calif.-based Geron last April disclosed in an SEC
fi ling that the assets related to the program were taken over
by Asterias Biotherapeutics Inc., a subsidiary of regenerative
medicine specialist Biotime Inc., of Alameda, Calif. The deal
involved transfers of common stock and warrants, along
with patents, regulatory fi lings and investigational new drug
applications fi led with the FDA for Geron’s Phase I safety
study with the cells. (See BioWorld Today, Jan. 26, 2009, Jan.
27, 2009, and April 5, 2013.)
“The mechanism of action by the cells, even though it’s the
same cells, is a little different [in spinal cord injury, where]
the idea is literally to build new circuitry to bridge the gap,
to bring function back to paralyzed patients,” Garr said. “In
ALS, even though patients lose their ability to walk, it’s not
because there’s a break in the signal coming down the spinal
cord from the brain. It’s because the muscles have atrophied
and died. Our main goal here is to improve the quality of life
and extension of life for these patients, is to keep them off
breathing machines for as long as possible.”
Neuralstem’s shares have been on the climb for about a
year. ”We don’t really talk about the stock that much,”
Garr said, because market changes are too hard to explain,
in most cases. “The clear answer is, there’s no substitute
for human data,” and interim data have been showing up in
presentations.
“A publication is coming out, we expect, on the Phase I trial [in
ALS],” he said. “Some of the patients went public, and it was
in Newsweek. It was pretty clear, just from a lay perspective,
they were seeing a defi nite benefi t to a number of patients, and
long term, not just marginal but signifi cant, quantitative actual
improvement that no one has seen before, and that has lasted
a very long time.”

Decreasing Progression, Increasing Function

A small Phase I ALS study is getting big results with stem cell treatment.

By Zac Haughn, Senior Associate Editor

http://bmctoday.net/practicalneurology/2013/10/article.asp?f=decreasing-progression-increasing-function#

For neurologists who see amyotrophic lateral sclerosis patients (ALS), techniques for coping and support take up far more room in a doctor’s bag than treatments and drugs. Significantly improving quality of life is as tantalizing as it is far away. Except for a small group of patients receiving human fetal neural stem cells in a small Phase I study: Six study patients experienced a stable, very slowly progressing or improved disease course at more than approximately 700-to- 850 days post-surgery. The trial’s most impressive responder couldn’t walk without a cane before his treatment of one million cells—500,000 on either side of his lower spine; after several months he walked unaided in a 2.5 mile walk-a-thon.1

The company behind the study, Neuralstem, Inc., says their stem cell technology enables the production of neural stem cells of the human brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells constitutively into mature, physiologically relevant human neurons and glia. They received FDA approval to commence a NSI-566/ALS Phase II trial in April 2013, following conclusion of the Phase I trial to test the safety of its stem cells and transplantation surgery in patients with ALS in February 2013.

The Phase I safety trial enrolled 18 patients. The trial began with 12 late- to mid-stage ALS patients who received a series of injections in the L2-L4 lumbar region. The first six patients were all non-ambulatory with permanent paralysis. Of these, the first three patients were treated with five unilateral cell injections, while the next three patients received 10 bilateral injections in the same region. The trial then progressed to patients who were ambulatory. The first three of these received five unilateral injections. The next three patients received 10 bilateral injections in the same lumbar region.

The aforementioned six study patients who experienced positive results shared two common clinical characteristics. They had no bulbar features of ALS, a form of the disease that destroys motor neurons in the corticobulbar area of the brainstem in the early stages and typically progresses faster than the limb-onset ALS. Additionally, these patients all received stem cell transplantation early in the course of their disease (at an average of two years, one month after symptom-onset). Two of the patients showing stabilization or improvement were among the three to receive transplants in both the lumbar and cervical regions.

Of the nine remaining patients in the trial, three subjects had a long disease course (5.6, 11.6 and 12.7 years of known disease), at the time of their transplantation, likely representing atypical ALS, and have had little change in the trajectory of their disease. Finally, six of the trial patients died of their disease, seven-to-30 months after surgery. Two of these patients had features of bulbar ALS at the time of their transplantation.

The NSI-566/ALS Phase II dose escalation and safety trial will expand to two centers. The trial is designed to treat up to 15 patients, in five different dosing cohorts, increasing to a maximum of 40 injections, and 400,000 cells per injection based on safety. (Phase I topped out at 15 injections of 100,000 cells each.) The first 12 patients will receive injections in the cervical region of the spinal cord only, where the stem cells could help preserve breathing function. The final three patients will receive both cervical and lumbar injections.

Neuralstem received approval from the FDA to move into the cervical (upper back) stage of the trial in the fall of 2011. The first of six patients in the cervical cohorts to receive stem cells was treated on November 18, 2011, which marked the first FDA-approved intraspinal surgical transplantation of stem cells into the cervical region. The trial then advanced to the final cervical cohort of three patients. The FDA approved the return of three patients from earlier cohorts to receive cervical transplants, making them the first to receive stem cell transplantation in both the lower and upper parts of their spinal cord. The first of these were treated in June 2012 and received five stem cell injections into the cervical region of the back, for a total of 15 injections, including the 10 lower-back injections previously received. The last patient in the Phase I trial was treated in August 2012. The trial was designed as a safety trial to treat 18 patients, and conclude six months after the final surgery.

For more on the team’s work, Practical Neurology talked to Eva Feldman, MD, Russell N. DeJong Professor of Neurology, Director of the A. Alfred Taubman Medical Research Institute, and Director of the Program for Neurology Research and Discovery at the University of Michigan, and Karl Johe, PhD, Neuralstem Chief Scientific Officer and developer of the cells used in the trial.
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Can you talk about your Phase I findings and the data you presented at the Canadian Neurological Sciences Federation Congress?

Dr. Feldman: As we continue to analyze data from Phase I of our trial, we continue to be pleased with the results. While the trial was designed to test the safety of direct intraspinal injections of stem cells in patients with ALS, we have found that a subset of patients have shown little progression of their disease, in some cases more than two years since surgery.

As we have reported, these individuals had no bulbar features of ALS and surgical transplantation occurred early within the course of their disease (average of two years and one month after symptom onset at the time of surgery). These very preliminary results suggest that intraspinal stem cell transplantation of ALS subjects with no bulbar symptoms early in the course of their disease could slow disease progression.

The FDA recently approved your Phase II trial. What are your objectives and what do you hope to learn?

Dr. Feldman: Our goal for the second phase of the trial is to continue to demonstrate the safety of the cells and of our methodology. We have designed this phase of the trial to further measure efficacy of the treatment and to deliver more stem cells with each operation. Our ultimate goal is to accumulate sufficient safety data and positive exploratory endpoints to progress to a widespread Phase III trial to test the efficacy of this new therapy in a larger cohort of patients.

What are the challenges facing stem cell therapy in ALS?

Dr. Feldman: We have taken great care to design the trial so that the surgery is unlikely to compromise the remaining function of ALS patients who enter the trial. The challenge is three fold. First, can we continue to safely deliver these stem cells to the spinal cord? Second, because this is a different type of transplant compared to larger whole organ transplants (like for example a heart or kidney), can we discontinue transplant rejection drugs after a period of initial administration? And, finally, the third and key question: Can we measure efficacy of our treatment, i.e. in the simplest of terms, does stem cell therapy work in ALS patients?

Can you talk about cultivating human fetal neural stem cells? How are they different than embryonic stem cells?

Dr. Johe, Chairman of Neuralstem: Neuralstem’s FDA approved cGMP cell banks are cultured in serum free medium. The cells have a mitotic capacity of roughly 60 doublings, so unlike ES cells, they are not “immortal.” The cells constituitively differentiate into regionally specific and relevant phenotypes; they do not have to be “driven” to their desired fate unlike ES cells. This makes for a more robust and efficient and predictable manufacturing process. ES cells for instance need to be “driven” to a specific neural precursor fate, as opposed to their many other potential fates, then culled for purity/safety purposes. Our culture methods start with the right neural stem cell for a particular purpose.

  1. Fox, C. FDA-approved Stem Cell Trial Dramatically Slows ALS. Biosciencetechnology.com; 2013-05-30.

ALS Stem Cell Therapy: Too Soon to Tell

Meeting Coverage

ALS Stem Cell Therapy: Too Soon to Tell

http://www.medpagetoday.com/MeetingCoverage/ANA/42288

Published: Oct 15, 2013

By John Gever, Deputy Managing Editor, MedPage Today

http://www.medpagetoday.com/MeetingCoverage/ANA/42288

NEW ORLEANS — Phase I results of a neural stem cell treatment for amyotrophic lateral sclerosis showed hints of promise but solid evidence of efficacy will have to wait for the next round of tests, a researcher said here.

Among 15 patients receiving stem cell injections into their spinal cords in the dose escalation study, nine have survived and the three receiving the most extensive injections showed stabilization of functional scores after almost 2 years of follow-up, said Eva Feldman, MD, PhD, of the University of Michigan.

The treatment also appeared to be safe, with no evidence of spinal cord damage resulting from the procedures or other major complications, she told attendees at the annual meeting of the American Neurological Association, of which she is president.

But “whether there is a benefit, we simply don’t know” from this small trial, said Feldman.

Phase II studies testing larger stem cell doses have recently begun, with the first three patients having undergone procedures at Feldman’s clinic and at Emory University in Atlanta. Her report here was the first to provide full phase I results, which have also been submitted for journal publication, she said.

There is currently no disease-modifying treatment available for the neurodegenerative disease that affects motor neurons in the spinal cord. A few symptomatic therapies are used but they are only modestly effective.

The influences that http://respitecaresa.org/job/directcarestaff/application-11-17/ order generic cialis existed before the success of the treatment and some of them are really cheap are having 100 percent success rate since their release in the market. The doctor diagnoses and treats sildenafil india wholesale various conditions and their treatment can lead to ED such as anti-depressants : TCA (tofranil/pamelor), SSRI, chlorpromazine and valium barbiturates.Kamagra – An erectile dysfunction treatmentKamagra tablets are produced by Ajanta Pharmacy. Tamoxifen serves like an estrogen receptor antagonist in breast tissue and its commonly used for the preparation of this particular capsule are clinically approved by health experts. cialis no prescription This ayurvedic plant can be taken vardenafil 20mg tab as a dietary supplement. With stem cell therapy, the goal is, at a minimum, to prevent further neurodegeneration and disability progression. In the work reported by Feldman, the source material is a proprietary line of neural stem cells developed by Neuralstem. of Rockville, Md.

These cells are capable of self-renewal and also differentiating into both glial and neuronal progenitor cells. The former differentiate further into astrocytes and oligodendrocytes, while the latter may develop into functional neurons.

Extensive preclinical work in rodents and, later, pigs established that preservation of spinal cord function after mechanical and/or chemical injury could be achieved with the stem cells, and that the spinal cord injections could be done safely, Feldman said.

She said the exact mechanism of benefit remains unclear, but the animal studies suggested that the stem cells act to protect and preserve endangered nerve synapses in the spinal cord. “It’s definitely not replacement” of destroyed synapses, she said.

The human tests began in 2010 with three patients with advanced nonambulatory ALS, who received injections on one side of the lumbar spine. A second nonambulatory cohort received bilateral lumbar injections.

Feldman and colleagues then advanced the trial into ambulatory patients, with three-patient cohorts receiving unilateral lumbar and cervical injections.

The final cohort of three patients received bilateral lumbar injections followed about 18 months later by unilateral cervical injections.

Except in that last cohort, efficacy outcomes were mixed. Six of the 12 patients in the earlier cohorts showed relatively steep declines in revised ALS Functional Rating Scale (ALSFRS-R) scores, while declines were slower in the others. But scores remained essentially the same as at baseline — in the range of 32 to 45 points — in the three patients receiving both lumbar and cervical injections.

One theme emerging from the earlier cohorts was that patients with bulbar signs “did not do well,” Feldman said.

Autopsy findings in phase I participants who died indicated that the stem cells had survived in these patients and that there was no suggestion that the therapy had played a role in their deaths.

In the phase II study, the first groups of patients received 200,000 cells per injection, with five injections per patient along the spinal cord on each side — a total of 2 million cells. Subsequent cohorts will receive 10 injections per side and with more cells per injection, reaching an eventual total dose of 8 million cells.