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A Better Pill to Swallow

http://www.bethesdamagazine.com/Bethesda-Magazine/November-December-2013/NSI-189/

A Better Pill to Swallow

A writer’s search for an alternative to antidepressants leads him to an unassuming office in Rockville and a potential miracle drug dubbed NSI-189

By David Frey

What if everything we thought we knew about treating depression was wrong?

What if the phalanx of antidepressants we’ve developed over the past four decades with optimistic names full of X’s and Z’s—Prozac, Zoloft, Paxil—was missing the mark?

What if there was a new treatment that could change our lives? That could enable those of us suffering from depression to stop swallowing that bitter pill every morning? That could undo the ravages not only of depression but of dementia, Alzheimer’s disease and the downhill slide of ordinary aging?

What if there was a drug that all of us might take someday?

I have personal reasons for asking. Seven years ago I shut down. Amid a crumbling marriage, I became emotionally paralyzed, unable to work, to write, to move. Emails and voice mails piled up unanswered. Slicing an avocado could leave me inexplicably sobbing. Then one day I stopped crying altogether. I went numb. Like so many other depression sufferers, I wondered if death might be easier. The thought scared me.

After five months of seeing a therapist with mixed results, I went to a doctor and walked away with a prescription for 10 milligrams of Lexapro, a cousin to Prozac. I had resisted turning to medication, but it helped.

Twenty milligrams helped even more. It didn’t make me feel good, but it made me feel less bad. It was a treatment, not a cure.

Yet a cure may be emerging at an unassuming office building in Rockville just 5 miles from my home.

Researchers at Neuralstem Inc. hope to eliminate depression by growing new neurons in the hippocampus, a part of the brain associated with memory and mood, a place deep inside the hemispheres where how we think and how we feel are neurologically entwined. Even the name of the process—neurogenesis—bridges science and the divine.

The company is in the midst of a three-round trial of a drug known as NSI-189. In development since 2000, the compound has shown success in mice, increasing the number of neurons in the hippocampus by as much as 20 percent. Now Neuralstem is conducting the first tests on humans.

“It’s quite revolutionary,” says Paul Currie, a neuroscientist at Reed College in Portland, Ore., who has followed recent scientific strides in understanding neurogenesis, the process by which neurons are generated.

Currie cautions, though, that researchers might be moving too fast, and that human trials could be premature. “It’s pretty exciting, but with excitement comes sometimes irresponsibility and overexaggeration, because we’re always looking for that magic bullet,” he says.

Until the ’60s, scientists believed neurogenesis was impossible. The brain was caged inside the skull with no room to grow. Then they discovered that new neurons were being generated inside the hippocampus, possibly to help us process new memories. It was a bright spot in an otherwise grim view of the brain. Cut your finger and it heals. Break your leg and it mends. Even blood refreshes itself. Except for the hippocampus and maybe a few other isolated areas, the brain has a set number of neurons, and they’re dying every day.

“That’s why brain damage and brain diseases are so horrible,” says Richard Garr, the 60-year-old Potomac resident who is Neuralstem’s president and CEO.

Neuralstem’s gambit is that it can treat not just the symptoms of depression but the very cause by developing a drug that intentionally grows new neurons in the hippocampus. Located deep within the temporal lobe of each hemisphere, the hippocampus takes its name from the scientific designation for the sea horse, which it resembles. Like Alzheimer’s patients, depression sufferers show damage there. A growing body of evidence suggests that antidepressants such as Prozac help repair the damage by creating new brain cells. They do it slowly, though; it’s not what they were designed to do. Neuralstem hopes to speed up the process with a specifically targeted drug.

“People use words like transformative a lot when they shouldn’t,” Garr says. “But if we’re right and it does work, this is completely transformative.”

At a world stem cell conference in London this past May, users of the biotech web platform Total BioPharma placed Garr at No. 15 among the 50 most influential people working on stem cells today.

With his short silver hair and narrow face, Garr looks disconcertingly like Roger Sterling, the disaffected ad executive on AMC’s Mad Men. He sits at a tidy desk decorated with models of dissected brains and spinal columns. Tiny, rectangular glasses nearly disappear on his face, and he speaks softly, interrupting his own thoughts by asking, “Right?” to make sure a listener follows along. He is the business side of Neuralstem. Karl Johe, the company’s chief scientific officer, heads up the research end.

A real estate attorney by training, Garr has come to know a lot about how the brain works. Twenty-two years ago, his only son, Matthew, developed a brain tumor. Matthew was just 4 years old, and Garr found himself navigating the complex geography of the human brain and the complications that can result both from a tumor and from the imperfect process of removing it.

Matthew survived, thrived even, but the experience affected him. Now 26, he has trouble remembering, and although he has a driver’s license, he doesn’t feel comfortable behind the wheel. A few years ago he nearly died when fluids that doctors left behind from the removed tumor created complications. They weren’t worried about removing all the fluids, Garr says, because “he wasn’t expected to live this long.”

After a difficult recovery from surgery, Matthew started kindergarten a year late at the McLean School in Potomac. There he became best friends with a new classmate named Arthur Johe. Meanwhile, Garr became friends with Arthur’s father, Karl, a scientist at the National Institutes of Health in Bethesda.

Karl Johe was pursuing a question tangentially related to Garr’s recent struggles with Matthew’s tumor: He wanted to know how something as simple as a fertilized egg can create something as complicated as the brain.

“I was trying to capture a way to study that moment of switch from being simple to becoming complex,” Johe says. “If we could understand that process, or glimpse into it, then maybe we could learn about how the brain functions.”

Johe’s question led him to discover neural stem cells. It also unlocked what he hoped could become a treatment for an array of brain disorders. Unlike fetal stem cells, which hold medical promise because scientists can transform them into any cell in the body, neural stem cells only become brain or spinal cord cells. That specialization is their strength, but because they’re also derived from fetuses, they are no less controversial.

“At the time, there was a ban on fetal tissue,” says Johe, now 52 and living in Miami. “At NIH, being the federal government, there was an imminent danger that I could not continue the research.”

Johe was also frustrated by academia and the various agendas of organizations offering research grants. If he wanted to use neural stem cells to find cures, he decided, he needed to form a company.

“Yes, there is a capitalistic motivation,” Johe says, “but the efficiency of achieving the goal is much higher in the private sector. In the private sector, the goal is crystal clear. In an academic setting, that’s not so clear.”

In 1997, the two men partnered to create Neuralstem in a Montgomery County business incubator. Cutting-edge research at NIH and Johns Hopkins University had made the county one of the nation’s top biotech centers. Neuralstem remains there, sharing the building on Great Seneca Highway with GeneImmune, Bethesda Pharma and similar companies.

“Like all parents who are faced with a child’s serious illness, you think about things like research and wonder how you can help, even if it will not help your child,” Garr says. “I felt that this was an opportunity to get involved in a very real way with a technology that could someday be very important for lots of people.”

Sixteen years later, Neuralstem is a “near-virtual” company, with just 16 employees split between Rockville and a San Diego lab. Thirteen years ago, the company went public with the ambitious stock ticker symbol “CUR.” It’s also leading human trials to treat stroke patients in China, with more planned in countries as far-flung as Mexico and Malaysia.

“We have patients all over the world, and we envision what we call a ‘near simultaneous’ worldwide rollout,” Garr says. The company has secured patents on its compounds worldwide. In many countries, Garr says, trials move faster and cost less than in the United States without sacrificing world-class science.

“How can you not be doing work all over the world?” he asks.

Before its work with the brain, Neuralstem established itself as a leader in repairing spinal column damage. It’s best known for its work in treating Lou Gehrig’s disease. Formally called amyotrophic lateral sclerosis, or ALS, the disease weakens muscle function in the lungs until it suffocates its sufferers.  Neuralstem set out to attack ALS by injecting spinal cord stem cells into the spine.

About half of the company’s money and time is still devoted to the creation of its ALS treatment. In 2011, Ted Harada, a former FedEx manager from Atlanta, became a minor celebrity when he made the rounds at CNN and CBS, proclaiming that his disease had receded after he took Neuralstem treatment NSI-566 in Phase I trials.

All the ingredient, power, dose are the same and the side effects also are the same of the both. levitra samples People http://pamelaannschoolofdance.com/competition-team-information/ generic viagra want to buy drugs online to save their time and efforts. If you suffer from penile dysfunction or any of the above mentioned conditions, it is time to choose the measurements of levitra generika 40mg . Here is free cialis without prescription a quote from the official product information for many medications containing finasteride mentioning the possible risk of breast cancer. This past May, the company announced that its drug had virtually halted ALS over the course of two years in six test subjects, including Harada, who has stopped using a walking cane. Last year, Harada was strong enough to take part in a 2½-mile ALS walkathon, a remarkable victory against a disease that can kill in two years. The FDA has approved Phase II trials for the drug at centers in Atlanta and Ann Arbor, Mich., where patients will be given as many as 40 injections of up to 400,000 cells each directly into the spinal column.

The company’s work with depression was serendipitous. Working with neural stem cells meant growing lots of tissue to test various drugs. That process, the company discovered, had other uses.

In the late ’90s, the Clinton administration sought to create a “super soldier” who could stay awake and alert for a week at a time. Neuralstem won a contract to work on the “warfighter of the future” project, Garr says.

The company wasn’t focused on creating a drug to keep soldiers awake, however; rather, it was interested in dealing with the consequences of long-term wakefulness. Without sleep, we become irritable, forgetful, irrational—all outward signs of the cell damage that can occur in the sleep-deprived hippocampus.

The Defense Advanced Research Projects Agency (DARPA) eventually canceled the project, Garr says, but Neuralstem moved forward, and NSI-189 was born. If the drug could help sleep-deprived soldiers, as its tests on mice had suggested, then maybe it could help others experiencing cell death in the hippocampus. Maybe it could treat depression, Alzheimer’s, even aging. As we get older, we all lose hippocampal cells. Could this drug make us super seniors?

“Yes,” Johe says. “There’s no question that degeneration of the hippocampus and other parts of the brain is part of the aging process. As we now take many different food supplements to counter or slow that aging process, I see this as a potential ‘vitamin for the brain’ to slow down or counter that aging process in our mental capacity.”

Currie, the Reed College neuroscientist, remains skeptical, however. “The human brain has taken how many millions of years to evolve? I don’t think it’s as simple as, ‘Well, we can improve it,’ ” he says.

Some 27 million Americans like me take antidepressants, according to researchers at Columbia University and the New York State Psychiatric Institute, which published their findings in the Archives of General Psychiatry in 2009. That’s one in 10 people lining up at the movies, driving the Beltway, sampling cheese at the farmers market. More women than men, more whites than African-Americans. And the number is growing.

Is it because depression is being diagnosed more often? Because antidepressants work better than before? Because pharmaceutical companies pressure doctors to prescribe them? Are we more stressed out? More isolated? Are we looking for a quick fix?

Nobody knows for sure, Currie says, but the answer is probably yes to all those questions.

Equally perplexing is why the United States, one of the world’s wealthiest countries, has one of the world’s highest rates of depression. In a 2011 World Health Organization study of 18 countries, only France, land of joie de vivre, had a worse case of the blues, with 21 percent of the population reportedly suffering from depression, compared with 19.2 percent in the United States. South Africa’s rate was half that of the U.S. In Montgomery County, according to a 2009 Centers for Disease Control survey, 16.8 percent of residents reportedly had been diagnosed with a depressive disorder.

Is depression a disease of the privileged? “We just don’t know,” Currie says.

My own depression is relatively mild. I managed to smile and even laugh, so friends and family members didn’t know there was a problem until I told them.

But there definitely was a problem.

A few months into the onset of my depression, I was walking with my dog into a snow-covered field at twilight. The sun had set, and the snow reflected the gray-blue light. Everything around me was a pallid veil. This is what depression looks like, I thought. It felt like I had crawled under a 50-pound blanket and I couldn’t lift it off.

For a while, talk therapy helped, but it didn’t push back the darkness. Mindfulness meditation made it easier to live with, but didn’t lessen it. Medication, however, lifted the veil. I could divorce, remarry, move, start over, get a second chance. Medication was life-changing for me.

Even leading researchers don’t entirely know why the drugs work, however. We do know that the brain fires impulses from neuron to neuron by way of a number of chemical messengers called neurotransmitters. One of these is a chemical called serotonin. One neuron fires a shot of serotonin across the synapse, the chasm between neurons. The next neuron takes up the message, and the sending neuron recycles the serotonin to do it all again. Prozac and similar drugs called selective serotonin reuptake inhibitors (SSRIs) block that reuptake process, keeping more serotonin at play between the neurons, and apparently boosting the mood-elevating signal.

But what does serotonin do? Unlike other brain chemicals—oxytocin, for instance, which we release during sex; or endorphins, which convert pain into pleasure, like a runner’s high—serotonin doesn’t seem to be a happy-making chemical. So why do drugs that keep more serotonin in our brains seem to make us happier?

Recent studies of neurogenesis suggest it may not be antidepressants’ effect on serotonin that makes the difference. Studies on mice have shown that depression symptoms coincide with hippocampal damage.

Antidepressants seem to heal that damage. A 2010 Columbia University study found that blocking the healing process prolonged depression, suggesting that without neurogenesis, antidepressants don’t work.

That’s where Neuralstem comes in with its potential wonder drug aimed specifically at rebuilding neurons in the hippocampus.

Like Currie, Lois Winsky, a pharmacology research chief at the National Institute of Mental Health in Bethesda, is reserving judgment of the drug until test results are available and Neuralstem reveals how its stew of organic chemicals works. But she notes that creating new cells isn’t necessarily enough. Those cells have to survive and integrate themselves into circuits that affect mood. It’s not clear if neurogenic drugs can make that happen, she says.

And while dead neurons seem linked to depression, it’s not clear how or why. Losing neurons doesn’t seem to directly cause depression, and more neurons don’t necessarily translate into more happiness. And that’s just in mice, Winsky says. We still don’t know what happens with people.

Even so, other companies are moving in a similar direction, though Neuralstem is the closest to bringing a neurogenic drug to market. Dr. Andrew Pieper, a psychiatrist at the University of Iowa, is also working on a drug to spur neurogenesis. His compound has only been tested on mice, with promising results, but he’s searching for a partner to develop it further. He’s interested in seeing what happens at Neuralstem.

“I really hope their compound works,” he says. “It would fill an important, unmet need for patients. Although some doctors and scientists don’t believe that neurogenesis can be critically involved in depression, we simply won’t know the answer until the hypothesis is tested. I’m eager to see the outcome of their clinical trials.”

Pieper says his compound works by keeping existing cells from dying, allowing more newborn neurons to become integrated into the hippocampus. It also seems to protect cells in other parts of the brain and in the spinal column, possibly offering treatments for Parkinson’s disease and ALS, as well as depression.

“The fact is, the current treatment options for patients with depression simply aren’t good enough,” Pieper says. “Many people are resistant to the effects of the current classes of antidepressant medications available, so we need new treatment options for patients suffering from depression.”

Neurogenic drugs like his or Neuralstem’s may be used alongside antidepressants. Or they may replace them, offering hope to people for whom antidepressants don’t work.

In 2011, 41 patients took Neuralstem’s NSI-189 during a seven-day safety trial. They showed no side effects, Garr says. That paved the way for the Food and Drug Administration to permit further Phase I testing, with 24 otherwise healthy depression sufferers taking increasingly higher doses in three rounds of tests at a center in Glendale, Calif.

In the first round, launched last year, healthy patients were given 40 milligrams a day for four weeks to test the drug’s safety. In the second, patients who were suffering from depression took NSI-189 twice a day. In the final round, due to wrap up this fall, depressed patients take three 40-milligram doses a day.

Throughout each 28-day trial, participants must stay at the center, watching TV or using the exercise facilities to pass the time while researchers monitor their brain activity daily and check their blood, urine and saliva.

Researchers give them MRIs when they show up, when they leave, and then four weeks and eight weeks later. It’s a double-blind study. Patients don’t know if they’re taking the drug or a placebo. Researchers won’t know the findings until all three rounds are complete.

If the results look promising and the FDA approves Phase II for NSI-189, Neuralstem will begin stretching the dosing to 90 days and expanding the number of subjects. The company may also launch additional trials involving patients with Alzheimer’s, dementia, traumatic brain injury and degenerative brain diseases.

Neuralstem is also working with members of the National Football League Alumni Association to develop a trial for treating ex-athletes. There have been a number of high-profile suicides among former players in recent years, some of whom had been diagnosed with traumatic brain injury. Lee Nystrom, a former NFL Alumni Association chairman and ex-Green Bay Packer, says his group is ready to start “pushing the envelope to create therapies” to help ex-players suffering from brain injuries that linger long after they’ve hung up their jerseys.

If the results of Neuralstem’s second phase are strong, a third phase would involve hundreds, maybe thousands, of subjects.  But even in the best-case scenario, Garr says, it will be five years before someone like me buys NSI-189 at the pharmacy.

Until that time, there are the standard antidepressants.

Over the years, I’ve taken ever-changing drugs and dosages. Ten milligrams of Lexapro, then 20. Forty milligrams of Celexa, Lexapro’s weaker sibling, then down to 20. A year ago I weaned myself off Celexa, chopping the pill into smaller and smaller pieces, and spacing the dosages farther and farther apart until I stopped altogether. I felt good. For a while. Then that familiar feeling returned. Dullness. Darkness. My body so heavy I couldn’t lift it. Thoughts so slow I felt I could grab them out of the air. I made it through six months before I needed to erase the pain.

Now I’m on antidepressants again. Every couple of weeks I grab a handful of pills and subject them to a pill cutter, a little guillotine that slices the pink ovals into two half moons. I take half a day. It’s an act of hope and submission. I still need you, I’m saying, but I only need half of you. One day, maybe, I won’t need you at all.

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U-M stem cell trial produces positive results for ALS patients

http://www.detroitnews.com/article/20130708/LIFESTYLE03/307080030/U-M-stem-cell-trial-produces-positive-results-ALS-patients?odyssey=tab|topnews|text|FRONTPAGE

Dr. Eva Feldman, a University of Michigan professor and neurologist, says the results of the stem cell clinical trial are extremely hopeful. (David Guralnick/The Detroit News)
When Ted Harada agreed to participate in a clinical trial testing stem cells in patients with Lou Gehrig’s disease, doctors warned him he could become paralyzed, or even die.
Instead, Harada experienced something almost unheard of in patients with an incurable disease: His symptoms improved.
As part of the trial led by a University of Michigan researcher, Harada had two surgeries in which 1.5 million stem cells were injected into his lower and upper spine.
Soon after the first surgery, Harada stopped using a cane. He regained strength in his arms and hands and even participated in a three-mile walk to raise awareness about Lou Gehrig’s disease, or amyotrophic lateral sclerosis, an aggressive, progressive neuro-degenerative disorder that affects the nerves and brain.
“We’ve all heard the slogan, ‘You can’t win the lottery unless you buy a ticket,’ ” said Harada, 41, who lives near Atlanta, Ga., with his wife and three children. “I am not a lottery player, but in this case I was. Maybe I will get lucky.”
Harada is among four patients who have either improved or stabilized in the closely watched clinical trial, the nation’s first to use stem cells in patients with the disease — named after the New York Yankees legend whose career was cut short by the disorder. Gehrig died in 1941 at age 37. The disease typically kills patients in three to five years. Only one treatment is available, and it extends life by just a few months.
The four patients who stabilized or improved in Phase I of the trial had two clinical features in common: At the time of surgery, they were early in the course of their disease — an average of two years and one month after the onset of symptoms. They also had none of the ALS symptoms known as “bulbarfeatures” — trouble speaking or swallowing.
Though preliminary, the results offer hope, said Dr. Eva Feldman, a University of Michigan professor and neurologist who is the trial’s principal investigator.
“The 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,” Feldman said. “I am extremely hopeful that we have found a way early in the course of the disease to make a true difference. Any treatment that can slow the progression of the disease is truly a home run for Lou Gehrig.”
ALS affects as many as 30,000 Americans at any given time, according to the ALS Association, a national nonprofit providing assistance to those with the disease.
The clinical trial was launched in 2010 with 15 patients at Emory University in Atlanta, and is expected to expand to U-M soon with 15 more patients at both locations for the second phase.
Although a small group of patients improved or stabilized during Phase I of the trial, five of them have since died from the disease. A sixth patient died of a congenital heart defect unrelated to ALS.
So, if you are a old age man levitra side effects with erectile problem, visit your doctor for prescription and at more affordable prices) online. Therefore, after the patent rights of the cheap india cialis you get the enduring sexual stamina that helps you to get relief from stress and focus on lovemaking. While, on one hand the customer base of this ED medicine is constantly viagra cialis generic increasing, on the other hand, numerous cases are coming up claiming it to be ineffective and useless for children’s and women’s to consume this herbal pill regularly two times with water to cure male sexual disorders or getting that discuss with partner or doctor. When folks are usually identified as Attention deficit hyperactivity disorder, on most occasions, these are currently being wrongly diagnosed which is basically because of generic tadalafil cipla disarray inherited plus much more. The other five patients in Phase I are still alive but had a long disease course before entering the trial, and do not represent typical ALS.
During the first phase of the trial, surgeons injected up to 1.5 million stem cells into either the lumbar, cervical or both parts of the spinal column, first in patients who could not walk and then in those able to walk. The doctors areinjecting fetal stem cells provided by Neuralstem Inc., a Maryland company.
Phase II will involve more injections and millions more stem cells and will focus on the upper portion of the spinal column, where nerve cells supply the diaphragm. When those cells are damaged, patients have difficulty breathing, which is a common problem in ALS patients.
Feldman, who is also president of the American Neurological Association, said she believes the stem cells played a therapeutic role in the small number of patients who stabilized or improved.
“The stem cells surround the sick nerve cells and help nurse them so they can remain more stable,” Feldman said.
At the beginning of the trial, Feldman stressed Phase I was an important step to determine if the stem cell treatments are safe. She recently reported the improvement of patients at a conference in Romania and is preparing to submit the results to a peer-reviewed journal.
It’s not unusual to hear about early results of a high-profile trial, but people should not read too much into it, said Steve Goodman, associate dean of clinical and translational research at the Stanford University School of Medicine.
“In an incurable disease with little hope, any glimmer of information that a useful therapy might be in the works is, of course, newsworthy, as long as release of such information does not compromise the treatment of current or future patients,” said Goodman, who is not familiar with Feldman’s clinical trial.
“That said, if the release occurs before efficacy and safety are well enough established, there is always the possibility that desperate patients outside the trial will clamor for the therapy, which can be dangerous in itself, or make future studies difficult. And of course, if there is a financial interest in disseminating results, that raises questions about both the motivation and ethics of raising too much hope on the basis of very early-phase results.”
In spite of experts who warn about early results leading to premature hope, those with loved ones who have succumbed to ALS are thrilled to hear there could be some movement in the future for better treatments.
Among them is Malcolm Beaton, an Allen Park resident who lost a father, two brothers and four sisters to the disease.
“Everything quits working but your mind. You know everything that is going on around you, but you cannot communicate,” said Beaton, 77. “It’s a horrible, horrible disease.
“God bless those scientists that are doing that research. If they come up with a cure, imagine how that would have affected my family. I might maybe still have my brothers and sisters here.”

From The Detroit News: http://www.detroitnews.com/article/20130708/LIFESTYLE03/307080030#ixzz2YTWGTZUx

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Human Stem Cells Help Acute SCI Rats; Chronic Trial Update

http://www.spinalcordinjury-paralysis.org/research/2013/05/31/human-stem-cells-help-acute-sci-rats-chronic-trial

Human Stem Cells Help Acute SCI Rats; Chronic Trial Update

Posted by Sam Maddox
Friday, May 31, 2013

A study was published this week showing that rats improved function after receiving transplants of Neuralstem, Inc.’s human neural stem cells three days after a spinal cord contusion injury (at L3). The study, “Amelioration of Motor/Sensory Dysfunction and Spasticity in a Rat Model of Acute Lumbar Spinal Cord Injury by Human Neural Stem Cell Transplantation,” was led by Martin Marsala, M.D., of the University of California, San Diego (UCSD) School of Medicine.

The human cells in this experiment — they call them NSI-566 cells — are derived from a single, legally aborted fetus; these are the same ones used by Neuralstem in 15 patients in an ALS safety trial. They are also the same ones set for clinical trial in chronic SCI, which we will get to in a minute.

In all cases, the cells are injected into the exposed spinal cord in several locations; so far, they appear to be safe. For the ALS trial, the company reported earlier this month that the procedure “was found to be safe, well-tolerated, and promising for other spinal cord conditions.”

The company also notes that some of the patients benefited from the cell transplants. A 39-year-old man with ALS, Ted Herada, got two sets of stem cell transplants. After the first, in 2011, he was recovered a meaningful degree of function, then declined. A year later, he got more cells. Neuralstem reports that Ted recently completed 2.5 -mile fundraising ALS walk in Atlanta, “still going strong past finish line.”  He is “Living a normal life: walking, climbing stairs, hands stronger again, increased dexterity.”

Says Principal Investigator Eva L. Feldman, M.D., University of Michigan, from a release, “Although this phase of the trial was not powered to demonstrate efficacy, we appear to have interrupted the progression of the disease in one subgroup of patients. We are anxious to move to future trial phases to examine therapeutic efficacy.”

Indeed, a Phase II trial with much larger cell dosage has been approved. From the company:

The Phase II trial is designed to treat up to 15 ambulatory ALS patients, in five different dosing cohorts, advancing up to a maximum of 40 direct injections and 400,000 cells per injection, based on safety. This compares to a maximum of 15 injections of 100,000 cells each, directly into the gray matter of the spinal cord, in the completed Phase I trial. The first 12 Phase II 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.


And yes, as we reported in January a clinical trial is being prepped for chronic spinal cord injury – for those one to two years post. It is expected to begin enrolling patients this summer as centers and institutional approvals are lined up. The company hasn’t released any information about the trial but a look at the trial detail at clinicaltrial.gov shows that several centers have been identified:

• Crawford Research Institute at the Shepard Center in Atlanta. Former Reeve Foundation International Research Consortium on Spinal Cord Injury Associate Keith Tansey, M.D., Ph.D. is listed as principal investigator for the study. (keith_tansey@shepard.org).
• University of Miami
• Thomas Jefferson University Hospital, Philadelphia
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• Karl Johe, the chairman and chief medical officer of Neuralstem, announced this week that UCSD Medical School would also be one of the trial centers. For more about this site, contact Adrienne Rebollo, arebollo@ucsd.edu.


I spoke with Johe: “The dogma has been that human cell transplants to the spinal cord were not feasible. First, the environment is too hostile, due to necrosis and inflammation. Second, there is no way to overcome this. We have shown here [in the acute rats], however, that our human cells integrate into the animals. Most of the stem cells die. Some survive and they proliferate in the injured area; they continue to divide until they fill the cavity. At that point they begin to differentiate into neural tissue.”

According to Marsala, the 556 cells appear to be doing two things: stimulating host neuron regeneration and partially replacing the function of lost neurons. “Grafted spinal stem cells are a rich source of different growth factors which can have a neuroprotective effect and can promote sprouting of nerve fibers of the host neurons. We have also demonstrated that grafted neurons can develop contacts with the host neurons and, to some extent, restore the connectivity between centers, above and below the injury, which are involved in motor and sensory processing.”



Johe said his 566 cells appear to reduce the size of injury. “Our studies with MRI show that the surface area of scar is much, much less. The stem cells also appear to stabilize the injury – the cells restore the integrity of the tissue. The fact the animals showed reduced spasticity is a sign of reduced  secondary damage,” said Johe.

“Rats often recover spontaneously,” said Johe, “so it is difficult to demonstrate a functional benefit; but the animals in our study have more accurate foot placement and better coordination of limb movement.”

Chronic SCI Trial

Johe wasn’t able to predict when this trial would commence – this summer, he hopes. He acknowledged that there has been great interest – the word chronic is extremely rare in SCI trials.

Johe thinks his stem cells are versatile and robust enough to make a difference in both acute and chronic SCI, stroke, even brain cancer. Stem cells, he said, are not like drugs, which might target a specific process or action. “Stem cells are more like a shotgun – they offer many possible actions and mechanisms. A plethora of effects will be required for a reconstructive treatment in the spinal cord.”

Here’s a summary of the chronic trial, from a release

This open-label, multi-site study will enroll up to eight patients with thoracic spinal cord injuries (T2-T12) who have an American Spinal Injury Association AIS-A level of impairment, between one and two years post injury. These patients exhibit no motor or sensory function in the relevant segments at and below the injury, and are considered to be in complete paralysis. Study patients will receive six injections in, or around, the injury site: the first four patients will receive 100,000 cells per injection; the second four patients, 200,000 cells per injection. All NSI-566 SCI patients will receive post-surgery physical therapy, as well as immunosuppressive therapy, which will be for three months, as tolerated. The trial study period will end six months post-surgery for each patient. The primary objective of the study is to determine the safety and toxicity of NSI-566 for the treatment of paralysis and related symptoms due to SCI. The secondary objectives are to evaluate graft survival in the transplant site by MRI, as well as the effectiveness of transient immunosuppression.

It is anticipated that each individual medical center will handle its own recruitment. We’ll pass along more information as it is available.

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Ted Harada: His ALS miracle continues to amaze

Crains Detroit Business
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Ted Harada: His ALS miracle continues to amaze

Stem-cell protesters are blind to the big picture

After stem cell injections, Ted Harada no longer needs his canes

You can understand Ted Harada being more than a little cheesed off when knee-jerk protesters start whining about embryonic stem cells and how it’s against God’s wishes and all that is moral and right to use them in the name of science.

But Harada is too busy still reveling in the seemingly miraculous improvement in his symptoms of ALS to be mad at anyone. Nothing is going to wipe that smile off his face.

Here’s the deal:

Harada, 40, is a former manager at FedEx who first noticed symptoms of ALS in 2009 while playing Marco Polo with his kids in the family swimming pool.

On March 9, 2011, he got an injection of 500,000 stem cells — the cells were derived by Rockville, Md.-based Neuralstem Inc. after a patient donated her fetus’ spinal-cord tissue in 2002 — as part of an 18-operation, 15-patient trial that last 2 1/2 years.

Harada doesn’t know if the tissue was from an embryo that was aborted or one that was miscarried or one that died as a result of an accident. The stem cells he got weren’t from that embryo, they were from cells that begat cells that begat cells that begat cells during 11 years and many generations of cells.

The operations were conducted by Emory University Hospital physician Dr. Nicholas Boulis. The trial was designed, in part, by Dr. Eva Feldman, director of the A. Alfred Taubman Medical Research Institute at UM and director of the ALS clinic at the UM Health System. Boulis is a former colleague of hers at UM.

Harada was one of three patients who got two rounds of injections, the second last August. Researchers monitored all patients for side effects, the trials proved to be safe and last month, the U.S. Food and Drug Administration gave its blessing for Phase 2 trials, to begin later this year in Ann Arbor and at Emory.

Signs of Harada’s ALS diminished noticeably after his first injection, and the improvement after his second injection was even more noticeable.

He hasn’t used his canes in months, his strong grip has returned, he easily walks upstairs to kiss his kids goodnight. On Oct. 20, he was even able to do a 2.5-mile fundraising walk in Atlanta to fight ALS.

“If the walk had been in July, I wouldn’t have attempted it,” he said. “After a third of a mile I would have been done. I would have sat down and said, `Someone come pick me up in a car.’ ”

Harada still has ALS. He still knows the likely prognosis is death. But there’s hope the prognosis of death won’t always accompany the diagnosis, now that there’s clearly some mechanism for improvement that researchers need to understand and refine.

“We’ve got to turn Lou Gehrig’s disease into Lou Gehrig’s chronic illness,” he told me last summer.

Today, Harada told me nearly all the improvement that happened after his last injection is still evident. Wednesday, he underwent his usual round of post-injection testing at Emory. “I’ve been doing great and feeling great. Just now, the left leg showed a little bit of weakness returning, but I’m still so much better than I was before the surgeries. It’s the first time, since August, they’ve noticed any slight weakness.

“It’s clear from the data that the injections reversed my symptoms and slowed down the progression of the disease. I’ve received a blessing. I almost forget I have ALS. I don’t have the constant reminder of having to use the canes. Now, I don’t think about ALS every day. Every couple of days something happens and I think, `Oh, yeah, I have ALS.’ ”

When Feldman told me the good news in April that the FDA had given its blessing for Phase 2 trials, she said Harada would be welcome to apply for another round of injections.

And Boulis briefly told him the same thing in Atlanta. But he and Feldman had overlooked an important detail: The trial protocol calls for patients who have been diagnosed within a certain window of time. Harada had been recently diagnosed when he got his first injection, and the thought, based on how well he did, is that those more recently diagnosed will show more dramatic results.

Alas, the irony is that based on his success, the change in test criteria now excludes him from further participation.

“I’d be intellectually dishonest if I said I wasn’t disappointed, but I’m still the biggest cheerleader for the trials,” he said. “If they can get good results and get to market, I might still be able to take advantage.”

The day after UM and Feldman happily announced Phase 2 trials would commence, loud and strident protesters showed up at UM to bloviate against the use of embryonic stem cells.

They were on TV, they were on the radio. Never mind that the embryo they were concerned about died 11 years ago and that this is a line of cells gathered legally in a process that obeyed all state and federal rules and is finally giving hope to people who no longer are sure their disease is a death sentence.

“I don’t think the protestors understand,” said Harada. “An embryo dying is a one-time tragedy, I know that. But this is a way to turn it into a gift. And it’s a gift that’s done so much good. That’s proved to be life extending.”

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Drug might treat depression, brain damage in athletes

Gazette.Net

Gazette.NetDrug might treat depression, brain damage in athletes

Friday, May 03, 2013

by Elizabeth Waibel Staff writer

http://www.gazette.net/article/20130503/NEWS/130509458/0/gazette&template=gazette

A Rockville company is conducting clinical trials on a drug it hopes could treat both depression and traumatic brain injuries in athletes.

The drug, developed by Neuralstem Inc., appears to rebuild a region of the brain that seems to atrophy in patients with major depression, according to a news release from the company.

This condition or inability to bear a child due to various reasons is known as infertility. levitra 10 mg When canadian pharmacy cialis considering making a purchase decision, you generally would like to seek advice from other people who have unhealthy livers suffer from chronic fatigue, sluggishness, irritability, anxiety, aches and pains and even cause issues irregular bowel movements. A new herbal medicine named diuretic and anti-inflammatory pill served as a quiet effective Chinese herbal medicine by extraction, concentration, drying and other processes refined single herb products. generic cialis mastercard Behavioural Strategies There are a number of behavioural strategies as well to address the issue of PE viagra for sale mastercard in men. Researchers believe the drug also might treat symptoms of traumatic brain injuries like those suffered by some professional football players who frequently take violent tackles and falls. Neuralstem is working with the National Football League Alumni Association to develop a clinical trial to treat ex-NFL players with symptoms of traumatic brain injuries.

“These injuries can result in long-term and serious loss of cognitive function, depression, a shorter life span and, sadly, death by suicide in some cases,” Richard Garr, president and CEO of Neuralstem, said in a statement.

During the past few years, the suicides of several ex-NFL players have drawn attention to depression as a possible symptom of traumatic brain injuries. A year ago, former NFL linebacker Junior Seau was found dead in his home of an apparent suicide.

After his death, scientists determined that he suffered from chronic brain damage. His family sued the NFL, The Washington Post reported, saying that he committed suicide because of brain disease caused by violent hits during football games.

Some research suggests that a region of the brain called the hippocampus might shrink in patients suffering from depression and in people with traumatic brain injuries, according to the news release. Based on tests in mice, researchers think the drug, named NSI-189, works by regrowing neurons and rebuilding the hippocampus.

Neuralstem researchers also think the drug might be able to help treat Alzheimer’s disease and post-traumatic stress disorder, but they have not yet done any trials to test that theory.

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Possible brain drug test

Possible brain drug test

  • NFL group, company hope to conduct new trial

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NFL alumni take stance on front line of effort to treat brain injuries

Newark Star Ledger

Newark Star Ledgerhttp://www.nj.com/jets/index.ssf/2013/04/nfl_alumni_take_stance_on_fron.html

Craig Wolff/The Star-Ledger

on April 25, 2013 at 4:30 AM

Wayne Clark

From time to time, Wayne Clark, once a backup quarterback in the NFL, pulls out his old team photo. San Diego Chargers. 1972.

His eyes fall to the young faces of long-ago teammates, and he is reminded that many of them ended up dying from the same cause.

Dementia, dementia, dementia, he finds himself muttering, a morbid chronicling of friends passing on, and, for Clark, a foreboding exercise. While no symptoms have appeared, last year Clark also was diagnosed with a disease that could one day rob him of memory and cognition and lead to profound depression — consequences that by now seem endemic to years of absorbing blows on the football field.

Learning that scientists wanted to enlist former NFL players for a clinical trial of a powerful new drug that could potentially reverse the course of certain brain injuries, Clark reacted without hesitation.

“I’d be willing to participate in anything,” he said. “And I’d expect all of us, no matter our present condition, would do the same.”

He is not alone.

Three weeks ago, the NFL Alumni Association, based in Newark and independent from the league and the NFL Players Association, sent a letter to thousands of old-timers, alerting them to the study of the drug, known for now as NSI-189. The drug holds the promise, its inventors say, of not merely treating the depression but regenerating parts of the brain that have suffered damage and even atrophied.

The responses from former players came in immediately: Count us in.

Amid a pitched legal battle with the NFL, these men say they are looking for answers not just from lawyers but from scientists. They are also mindful that a number of former players in the throes of depression and other mental disorders have committed suicide and their families have donated their brains for research.

Some of the players who committed suicide, including Junior Seau a year ago and Dave Duerson in 2011, shot themselves in the chest. Duerson seemed to think he could advance knowledge of chronic traumatic encephalopathy, known as CTE, from the grave. He left behind a suicide note requesting that his brain be used for research.

These new tests, the old players say, present a chance for former players to do a novel thing — assist the research while they are still alive.

Erectile dysfunction prevents men from leading a normal canada sildenafil sex life. Treatment services vary based on particular viagra price uk situations of the individuals. There are purchase levitra online certain Cheap Erectile Dysfunction Drugs Canada is an important site for providing relief to the affected people. Kamagra is not only a substance that enhances sexual desire but also create stimulation that is cheap viagra no rx required to develop erection. “What I’m excited about is that we are not placing blame,” said Lee Nystrom, who had a brief professional career with the Packers in the 1970s and is a former head of the alumni association. He has grown tired in recent years, he said, of players reduced to grousing about what they see as the league’s inaction over head injuries.

“I’m a positive person, and for once this is something positive we can do,” he said. “And it can help everyone, not just football players.”

The NFL faces a class-action lawsuit from more than 4,000 former players and their wives, who say that over years the league deliberately withheld findings which point to the affects on the brain from a violent game.

NFL spokesman Greg Aiello said the league has given millions to research into brain injuries, including $30 million to the National Institutes of Health.

“We have no issue with this,” Aiello said. “A lot of people are engaged in this. We support any research that would advance the understanding of concussion.”

The drug was created by Neuralstem, a Rockville, Md., company. The drug appears to help the hippocampus part of the brain replenish its own neurons. The hippocampus is vital for memory and a range of cognitive skills. Autopsies performed on former football players and others have found damage to this area of the brain.

Richard Garr, the research company’s president, said the new drug was given the go-ahead for the clinical trials by the Food and Drug Administration and already has passed through a first level of clinical trials. The players would be part of a second phase of tests. He said that unlike traditional antidepressants that address chemical imbalances, the new drug was found to reverse atrophy in laboratory animals.

The letter from the alumni group steered former players to Garr, who said he has received a stream of e-mails and phone calls.

“It’s pitiful,” he said. “Guys who are out there who have to program their addresses into their cars.”

Nystrom, he said, “wakes up every morning scared to death he won’t be able to remember his wife.”

Clark, the former backup quarterback, is 65. He found out he had CTE as part of a study last year at UCLA. Like many former players, he has come to appreciate the Rorschach-like images produced from brain images. He is thankful, he said, that he has not developed symptoms, but apprehensive about what the future may hold.

In all, he said, seven members of the 1972 Chargers suffered from dementia and other brain traumas. Two have died in the past year, he said.

“Is that the natural part of life?” he wondered. “Is that normal, or is playing football the reason? That’s why these tests are important.”

©  NJ.com. All rights reserved.

 

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Drug which could reverse depression symptoms draws interest of NFL Alumni Association

http://www.nj.com/sports/index.ssf/2013/04/nfl_alumni_association_to_invi.html

Drug which could reverse depression symptoms draws interest of NFL Alumni Association

Craig Wolff/The Star-Ledger
on April 24, 2013 at 9:47 AM

The NFL Alumni Association announced today that it has invited thousands of former players to take part in a test for a powerful new drug which holds the promise of reversing major depression symptoms and even regenerating damaged parts of the brain.

Amid a class action lawsuit over the effects of years of heavy hitting on the football field, the old-timers say they are now looking for answers not just from lawyers but from scientists. They are also mindful that a number of former players in the throes of depression have committed suicide, careful to avoid shooting themselves in the head, and that their families have donated their brains for research. These tests then, they said, present a chance for former players to assist the research while they are still alive.

Teenagers and their careless driving is a topic of speculation since cialis in uk online forever. Choosing the best online service provider will order viagra from india never ever make you disappoint in any aspect. Free of cost consultation services are available online because there is a risk of side effects if they are properly used at the suitable surface treatment levels, resurfacing action of Fraxel boost the cell proceeds and causes extrusion of the melanin pigment from the skin, as a result skin get rejuvenated appearance due to smoother touch and even pigmentation. 100mg viagra online He is a brilliant sexologist, known to provide the Best treatment at his penis enlargement clinic in cialis samples Delhi. “What I’m excited about is that we are not placing blame,” said Lee Nystrom, a former Green Bay Packer and until recently the head of the alumni group. He said he has grown tired in recent years of players simply grousing about what they see as the league’s inaction over the problem.

“This has the potential of not just helping players, but also everyone suffering from major depression.

The drug, known as NSI-189, was created by Neuralstem, a Maryland research company. The drug, still in early clinical trials, the researchers say, do something typical antidepressants do not — regenerate parts of the brain that have suffered damage and even atrophied. It can, they say, not only reverse depression symptoms but also the loss of cognitive abilities.

Richard Garr, the company’s president, said he hopes that former players will enlist for what are known as Phase 2 trials.

“Most antidepressants,” Garr said, “work on the balance of chemicals in the head.”

The new drug, he said, reverses the course of atrophy that may have been caused by trauma and injury.

Posted on

NFL Alumni Back New Drug to Keep Brain-Injuries From “Destroying Quality of Life”

 

http://www.latinospost.com/articles/17434/20130424/nfl-alumni-back-new-drug-keep-brain-injuries-destroying-quality.htm

NFL Alumni Back New Drug to Keep Brain-Injuries From “Destroying Quality of Life”

By Erik Derr | First Posted: Apr 24, 2013 04:13 PM EDT

(Photo : Reuters)

There may soon be a medication to counter the effects of sports- related head injuries.

Neuralstem Inc., a company that specializes in cell therapy technology, has developed a drug in pill form designed to stimulate neurons in the area of the brain that handles depression and may be a factor in major brain injuries.

The drug, currently designated “NS1-189,” is already going through a clinical trial for depression treatment.
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During studies on animal subjects, researchers saw how the drug seemed to stimulate the growth of brain cells, prompting the company to pursue additional examination of the potential use of the medication for concussion treatment.

Neuralstem today announced it will be working with the NFL Alumni Association to begin clinical trials of NSI-189 with former players.

The National Football League has expressed great concern over the development of neurological disorders in former players.

The increase in the league’s awareness of the issue follows a series of suicides linked to concussions players sustained during their careers — including that of Pro-Bowl linebacker Junior Seau, who took his life three years after retiring from a 13 years playing in the NFL.

“The National Football League Alumni Association is focused on this serious health issue, which is destroying quality of life and has tragically led to several high-profile suicides just this past year among our members,” said Lee Nystrom, Chairman of the Board, Emeritus of the NFL Alumni Association and a former Green Bay Packer. “The NFL Alumni Association is excited to be working with Neuralstem on this cutting-edge technology. We are committed to pursuing both basic research into traumatic brain injury as well as pushing the envelope to create therapies that can improve the quality of life for our members afflicted with these diseases.”

Said Richard Garr, Neuralstem’s president and CEO: “These injuries can result in long-term and serious loss of cognitive function, depression, a shorter life span and, sadly, death by suicide in some cases…In addition to finding ways to better prevent such injuries, it is imperative that we provide new and improved ways to treat those with such neurological trauma.”

NS1-189 has already received support from the Defense Advanced Research Projects Agency, as well as and the National Institutes of Health.

Posted on

Football and Concussions: New Drug To Be Tested On NFL Alumni

Medical Daily

http://www.medicaldaily.com/articles/14870/20130424/football-concussions-new-drug-tested-nfl-alumni-ns1-189-neuralstem.htm

Medical Daily

April 24, 2013 12:52 PM EDT

Football and Concussions: New Drug To Be Tested On NFL Alumni

Technology company Neuralstem Inc. is partnering with the NFL to begin testing of concussion medication on human subjects.

By Justin Caba

NFL

Finally, a possible solution to contact sport related head injuries.

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The National Football League (NFL) has expressed a great deal of concern lately when it comes to former player’s development of neurological disorders. The increase in awareness of the issue comes after a series of suicides were linked to concussions sustained during a player’s career, most notably Pro-Bowl linebacker Junior Seau, who took his life three years after retiring from a 13 year NFL career.

“These injuries can result in long-term and serious loss of cognitive function, depression, a shorter life span and, sadly, death by suicide in some cases, said Neuralstem’s president and CEO, Richard Garr. “In addition to finding ways to better prevent such injuries, it is imperative that we provide new and improved ways to treat those with such neurological trauma.”

The drug, currently called “NS1-189.” is already in Phase lb clinical trial for treatment of depression; however, in further studies on animal subjects researchers noticed the drug seemed to promote the growth of brain cells, prompting them to pursue additional studies in its potential use for concussion treatment.

On Wednesday, Neuralstem announced that it will be working with the NFL Alumni Association to begin clinical trials on NSI-189 with former players.

“The National Football League Alumni Association is focused on this serious health issue, which is destroying quality of life and has tragically led to several high-profile suicides just this past year among our members,” said Lee Nystrom, Chairman of the Board, Emeritus of the NFL Alumni Association, and former Green Bay Packer. “The NFL Alumni Association is excited to be working with Neuralstem on this cutting-edge technology. We are committed to pursuing both basic research into traumatic brain injury as well as pushing the envelope to create therapies that can improve the quality of life for our members afflicted with these diseases.”

NS1-189 has already received backing from both the Defense Advanced Research Projects Agency (DARPA) and the National Institutes of Health (NIH).