FDA Should Tread Carefully with Stem Cell Regulation

(Editor’s note: This week FDA commissioner Scott Gottlieb said the agency would crack down on clinics that offer experimental stem cell treatments. While acknowledging that stem cells offer “significant promise” for treating chronic pain and other chronic conditions, Gottlieb said some clinics were preying on sick people desperate to find cures.

A. Rahman Ford has received stem cell treatment and has been closely following developments in stem cell research and regenerative medicine.)

By A. Rahman Ford, Columnist

On its face, FDA Commissioner Gottlieb's statement seems like a reasonable approach to regulating stem cell therapies.  He emphasizes the need to balance costs and benefits, and the need to protect vulnerable consumers from exploitation. 

I think all can agree with the Commissioner when he states that "these technologies hold the potential to significantly alter the course of a broad range of diseases."  These diseases are often accompanied by intense physical pain that pharmaceuticals cannot relieve.

Specifically, the Commissioner makes three heartening observations. First, he acknowledges the "significant promise for transformative and potentially curative treatments" offered by regenerative medicine.  This is a promise that mainstream pharmaceutical medicine has yet to fulfill, and one that those suffering from chronic pain need addressed immediately. 

Second, it is without question that regulatory clarity and the resolution of legal uncertainty regarding these therapies' use can be a good thing.  If there are in fact an irresponsible "select few," or a minority of unscrupulous, exploitative "bad actors" as the Commissioner claims, then legal action by the FDA against them is reasonable. 

fda commissioner scott gottlieb

fda commissioner scott gottlieb

Finally, the Commissioner seems to implicitly recognize how critical it is for the FDA to respect the distinction between medical products subject to agency oversight, and those which fall under the "practice of medicine," a distinction which Commissioner Gottlieb acknowledges is fraught with "close calls."

That said, as an advocate for patients seeking stem cell therapies, upon reading Commissioner Gottlieb's statement I am overall circumspect.  It is well known that the FDA has a rather unsettling history of issuing regulations that unduly restrict patients' access to stem cell therapies, specifically autologous stem cell therapies.  These are therapies that use cells harvested from one person, are minimally manipulated, and then administered to the same person. 

I've previously made my position on this "personal" stem cell therapy known, particularly the privacy implications involved. 

Restrictions such as the unduly burdensome "minimally manipulated" federal standard and the "same basic function" requirement are clear evidence of an intent to restrict.  So, the fact that Commissioner Gottlieb's statement reiterates the "same basic function" standard as a factor in requiring that a stem cell therapy be approved through a clinical trial, rather than it being part of the "practice of medicine," seems to indicate more of the same federal overreach.

Make no mistake, the potential dangers of stem cell therapy are real, and proactive effort to protect patients is far better than any reactive effort.  However, the potential dangers should not be overstated or exaggerated ostensibly toward the end of more unnecessary restrictive regulation. 

The FDA has a history of doing this.  For example, the New England Journal of Medicine published a commentary in March by then FDA Commissioner Robert Califf arguing that, aside from a few indications, the clinical use of autologous stem cell therapies has not been proven effective and can even be dangerous. 

Not only did the article ignore years of clinical data from medical practitioners, the one cited example of the danger of autologous stem cells was actually an example of allogeneic stem cell use -- stem cells from another person!

bigstock-Asian-Female-Doctor-Or-Scienti-5696866.jpg

Thus, when the Commissioner asserts that the FDA will "aid in the effort to bring novel therapies to patients as quickly, and as safely, as possible," it simply belies history.  Likewise, overtures made toward any potential regulations being congruent with the 21st Century Cures Act are dubious.  The spirit of the Cures Act is clear; it calls for the "accelerated approval for advanced regenerative therapies." 

More federal regulation rarely, if ever, leads to acceleration of anything.  In fact, it almost always tends to slow things down.  Thus, unnecessary and unreasonably burdensome regulation by the FDA could contravene the will of Congress, and thus the will of the American people.

Texas Legalizes 'Personal' Stem Cell Therapy

Furthermore, the FDA's prospective regulatory guidance must be viewed in the context of recent events in Texas.  On June 13, Texas governor Greg Abbot signed HB 810 into law, which made Texas the first state to legitimize the use of personal stem cell therapies statutorily. The signing of the bill was celebrated not only by stem cell advocates, but by the countless Americans who suffer from chronic, debilitating conditions for which the current medical services delivery model can offer only surgery and medication.  For many, it was a monumental step forward toward fulfilling the promise of regenerative medicine and realization of true health care.  

However, the FDA may have seen this move as reinforcing a "wild west" stem cell landscape, a landscape which it believes it must police.

All of us, including FDA officials, should be reminded that on February 28, at President Trump's first State of the Union speech (and on Rare Disease Day), the President took note of Sarah Hughes, a young attendee who had used her own stem cells to successfully treat Pompe’s Disease. The therapy normalized her immune system, alleviated her symptoms and helped reduce her medications from 22 to 8.

We must also remember the promise President Trump made to America's military veterans, many of whom suffer from painful, debilitating conditions that may be treated or cured by stem cells.  President Trump cares deeply about veterans' health.  He recently signed the Veterans Appeals Improvement and Modernization Act, which streamlines the process of veterans appealing claims over disability benefits.  He also signed a bill that will let more veterans bypass the Department of Veterans Affairs and instead receive treatment from private doctors. 

Finally, he signed legislation approving new tools to expand the VA's existing Telehealth Services, so veterans can schedule appointments and have video consultations from their mobile phones.  It seems obvious that President Trump would never support restricting veterans' access to the medical care they need, including stem cells.

I believe that President Trump, through his devotion to our veterans, the Congress through the Cures Act, and the American people through their need for medical alternatives, would strongly disagree with any unreasonable curtailment of stem cell therapies. 

The FDA must not defer to the opinion of "industry," and must prioritize the needs of Americans like Sarah Hughes and our suffering wounded warriors.  People are in pain and pills can’t always help them.

.jpg

A. Rahman Ford, PhD, is a lawyer and research professional. He is a graduate of Rutgers University and the Howard University School of Law, where he served as Editor in Chief of the Howard Law Journal. He earned his PhD at the University of Pennsylvania.

Dr. Ford is not affiliated with any stem cell treatment provider. He suffers from chronic inflammation in his digestive tract and is unable to eat solid food.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

FDA Expands Crackdown on Stem Cell Clinics

By Pat Anson, Editor

The Food and Drug Administration is stepping up its campaign against experimental stem cell therapies, which are increasingly being used to treat cancer, diabetes, neuropathy, back pain and other chronic illnesses.

On Friday, the FDA raided two stem cell clinics operated by California Stem Cell Treatment Centers, and seized five vials of a smallpox vaccine supplied by StemImmune in San Diego. The vaccine is mixed with stem cells derived from a patient’s body fat – known as adipose tissue -- and then injected back into the patient. The FDA considers that “an unapproved and potentially dangerous treatment” for cancer.

On Monday, the FDA also sent a warning letter to a stem cell clinic in Florida, which advertises stem cells derived from body fat to treat a variety of chronic illnesses, including rheumatoid arthritis, lupus and other autoimmune diseases. Three elderly women at the clinic went blind after having stem cells injected into their eyes in an attempt to treat macular degeneration.

in a lengthy statement announcing the crackdown,  FDA commissioner Scott Gottlieb, MD, said stem cell therapy and regenerative medicine hold “significant promise for transformative and potentially curative treatments,” but some “bad actors” were preying on sick people desperate to find cures.

“There are a small number of unscrupulous actors who have seized on the clinical promise of regenerative medicine, while exploiting the uncertainty, in order to make deceptive, and sometimes corrupt, assurances to patients based on unproven and, in some cases, dangerously dubious products,” Gottlieb warned.

“In such an environment a select few, often motivated by greed without regard to responsible patient care, are able to promote unproven, clearly illegal, and often expensive treatments that offer little hope, and, even worse, may pose significant risks to the health and safety of vulnerable patients.”

stem cells.jpg

Dr. Mark Berman, a co-founder of California Stem Cell Treatment Centers, told the Los Angeles Times that Gottlieb’s comments were "disparaging and misrepresentative," and showed "a lack of understanding" of stem cell treatments. 

As PNN has reported, hundreds of stem cell clinics have opened around the country in recent years, often mixing hope with hype to make claims such as “You don’t have to accept chronic pain as a fact of life.”  The treatments are expensive and usually not covered by insurance.  A clinic in Sacramento, for example, charges $5,000 for a single joint injection and $6,000 for a spinal injection.

FDA officials say there is not enough evidence to support some of the newer stem cell therapies – particularly when cells are harvested from a patient’s own body fat (adipose tissue).

“Stem cells derived from sources such as adipose tissue are being used to treat multiple orthopedic, neurologic, and other diseases. Often, these cells are being used in practice on the basis of minimal clinical evidence of safety or efficacy,” wrote Robert Califf, MD, Gottlieb’s predecessor as FDA commissioner, in a commentary published in the New England Journal of Medicine.

Some patients, however, have reported remarkable recoveries from chronic conditions often deemed untreatable. Sara Bomar, for example, was confined to a wheelchair after being diagnosed with arachnoiditis, a painful inflammation of nerves in her spinal column. She started walking again after a high dose infusion of stem cells made from adipose tissue.

“I am able to walk. I am able to workout at the Y. I am still careful. It’s not like I don’t ever have any pain, I do have a little bit from time to time. But it is nothing compared to what I had before,” Bomar told PNN.

Gottlieb said the FDA would release new guidelines in the fall to outline what types of stem cell therapy and regenerative medicine would be allowed. And he warned that more enforcement actions were coming, like the ones in Florida and California.

“I will not allow these activities to go unchecked. I’ve directed the FDA to launch a new working group to pursue unscrupulous clinics through whatever legally enforceable means are necessary to protect the public health,” Gottlieb said.

Some patients who have the resources are heading to Europe to get regenerative treatments that can't get in the U.S.  The Seattle Seahawks this week sent five more players to Germany to have their blood processed and re-injected to treat nagging injuries. The procedure involves withdrawing blood from the patient and then spinning it to produce a high concentration of platelet cells. The plasma is then injected back into the patient at the injury site, speeding up the healing process. Two other Seahawks have already had the procedure, along with athletes such as Kobe Bryant and Alex Rodriguez.

Stem Cell Vaccine Could Reverse Arthritis

By Pat Anson, Editor

A team of researchers has successfully used gene-editing technology to “rewire” mouse stem cells to fight inflammation – a finding that could pave the way for a new class of biologic drug that replaces cartilage and protect joints from damage caused by arthritis.

The stem cells, known as “smart” cells (stem cells modified for autonomous regenerative therapy), were developed at Washington University School of Medicine and Shriners Hospitals for Children in St. Louis, in collaboration with investigators at Duke University and Cytex Therapeutics in North Carolina.

The research findings are published in the journal Stem Cell Reports.

"Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed," said senior author Farshid Guilak, PhD, a professor of orthopedic surgery at Washington University School of Medicine.

Guilak and his colleagues grew mouse stem cells in a test tube and then used a gene-editing tool called CRISPR to remove a gene that plays a key role in inflammation. That gene was replaced with a gene that releases a biologic drug that combats inflammation.

Within a few days, the modified stem cells grew into cartilage cells and produced cartilage tissue. Further experiments showed that the engineered cartilage was protected from inflammation.

"We hijacked an inflammatory pathway to create cells that produced a protective drug," explained Jonathan Brunger, PhD, the paper's first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

IMAGE CREDIT: ELLA MARUSHCHENKO

IMAGE CREDIT: ELLA MARUSHCHENKO

Many current biologic drugs used to treat arthritis – such as Enbrel, Humira and Remicade -- attack an inflammation-promoting molecule called TNF-alpha. But the problem with these drugs is that they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

"We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body," said Guilak. “If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint."

Researchers have begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases. If the work can be replicated in living laboratory animals and then developed into a clinical therapy, the cartilage grown from stem cells would respond to inflammation by releasing a drug that protects them from further damage.

"When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation," Guilak explained. "We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, it's possible we could make stem cells that would sense glucose and turn on insulin in response.

"The ability to build living tissues from 'smart' stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine."

Farshid Guilak and co-author Vincent Willard have a financial interest in Cytex Therapeutics, a startup founded by some of the investigators. They may license the technology and realize financial gain if it is eventually is approved for clinical use.

Guilak and his colleagues at Cytex have also used stem cells to grow new cartilage that could someday be implanted into arthritic hips, delaying or eliminating the need for hip replacement surgery.

Stem cells are found throughout the body and are increasingly being used to develop new treatments to repair damaged tissue and reduce inflammation. The Food and Drug Administration considers most stem cell treatments experimental because their safety and efficacy haven’t been proven through clinical studies.

Can Stem Cells Treat Arachnoiditis?

Pat Anson, Editor

Sara Bomar thought she’d be spending the rest of her life in a wheelchair or bedridden.

sara bomar davis and husband george

sara bomar davis and husband george

But the 54-year old Tennessee woman is not only walking again, she’s been able to resume her career as a doctor after an experimental stem cell treatment for her chronic back pain.

What makes her recovery all the more remarkable is that Bomar has arachnoiditis, a spinal disease that leaves many patients permanently disabled.  

“I am able to walk. I am able to workout at the Y. I am still careful. It’s not like I don’t ever have any pain, I do have a little bit from time to time. But it is nothing compared to what I had before,” says Bomar, who practices general medicine in the Nashville area.

Bomar’s back problems started in 2000 with a ruptured disc. Surgery, physical therapy, epidural steroid injections and spinal cord stimulators all failed to stop the pain and her condition worsened. By 2008, she was in a wheelchair and diagnosed with arachnoiditis, an inflammation of the arachnoid membrane that surrounds the spinal cord.

The inflammation causes scar tissue to build around spinal nerves, which begin to adhere or stick together. That is known as adhesive arachnoiditis, which causes burning or stinging pain that can be felt from head to toe. The disease is progressive and thought to be incurable.

Or is it?

Two years ago Bomar heard about innovative stem cell treatments being offered by Todd Malan, MD, at the Center for Regenerative Cell Medicine in Scottsdale, Arizona. At the time, Malan had successfully treated only one other patient with arachnoiditis, but in that case the disease was still in its early stages. Bomar’s arachnoiditis was more advanced, but she thought stem cells were worth trying.

“It was kind of a shot in the dark,” she says. “There was really nothing else.”

Stem Cells as “Seeker Hunters”

Most people think stem cells can only be found in bone marrow or human embryos, but Malan uses fat-derived stem cells found in the patient’s adipose (fatty) tissue.  When injected into the blood stream, Malan says these stem cells are “incredible seeker hunters” that can locate and repair damaged tissue, while reducing inflammation and improving circulation.

“The key is to understand that these stem cells are designed by the body to do this repair process,” Malan said. “What we’re trying to do with these procedures is to enhance the normal process that the body uses.”

Malan enhances the process further with a high-dose infusion of as many as 100 million stem cells. For patients with spinal cord or brain injuries, he also injects mannitol, a drug used to treat head trauma that apparently helps the stem cells pass through the blood-brain barrier into the central nervous system.  

In August 2014, Bomar received a high-dose infusion of her own stem cells through an IV in her arm. Within a week, she noticed that the blood circulation in her left leg seemed to be improving.

“My mom came and visited me three days after I had the procedure and she said, ‘You know, I think your foot looks a little pinker.’ And I looked down and said, ‘Gosh mom, you’re right.’”

A few days later, Bomar noticed reduced swelling in her feet and could put on shoes that she wasn’t able to wear before. Months later, she was able to exercise on an underwater treadmill and then an elliptical machine. There was also less pain.

“The pain started to lessen. It was slow, it wasn’t all at once. But over months, which I think was fantastic progress, that pain did lessen,” she remembers. “Arachnoiditis is a pain that you deal with constantly. And it was really something not to have that constantly. I remember at first just thinking, wait a minute. I don’t have any pain right now. That was pretty amazing.”

sara and daughter anna

sara and daughter anna

Bomar’s condition has improved so much that she was able to vacation with her family in California last summer, and go hiking and bike riding.

Because Bomar still has metal in a spinal cord stimulator implanted in her back, an MRI can’t be taken to confirm if the nerves in her spine are still encased in scar tissue. But Malan is confident the scar tissue is either gone or the stem cells have created enough healthy nerve tissue to bypass the problem.

“The studies have been well documented, especially for scar tissue breakdown,” he says.

Malan has now treated about two dozen patients with arachnoiditis, but is careful not to say that a cure or treatment has been found. He says more studies are needed to confirm if his stem cell therapies are safe and effective. 

“We have not had a patient yet who hasn’t had a clinical response,” he told Pain News Network. “The vast majority of the patients with adhesive arachnoiditis or chemical arachnoiditis have gotten to a point where they say their quality of life has significantly improved.” 

“I believe the doctor. I think it could be a breakthrough,” says Forest Tennant, MD, a California pain physician who is one of the world’s leading experts on arachnoiditis.

Tennant plans to begin using stem cell treatments himself, along with other experimental therapies such as growth hormones. But he doesn’t think stem cells will work on patients with advanced cases of arachnoiditis.

“I do have two patients who have tried it and it did not work. But their cases were so far along. They were already bed-bound and paralyzed, and you can’t expect a treatment like that to help,” he said. “The disease has to be in its fairly early stages for it to work, would be my guess. We don’t know enough. It’s the old story of one case does not make a treatment, but one good case certainly stimulates investigation into that treatment. And that’s where we’re at with this.”

More Clinical Studies Needed

One issue that’s been holding up investigation is that most stem cell treatments have not been approved by the Food and Drug Administration. FDA commissioner Robert Califf, MD, was openly skeptical of stem cells derived from body fat (adipose tissue) in a commentary recently published in the New England Journal of Medicine.

“Stem cells derived from sources such as adipose tissue are being used to treat multiple orthopedic, neurologic, and other diseases. Often, these cells are being used in practice on the basis of minimal clinical evidence of safety or efficacy,” Califf wrote.

Dr. Malan bristles at the notion there is not enough evidence and blames the FDA for holding up stem cell research.

“The FDA hasn’t approved a single stem cell technology in 16 years in the United States,” he said. “These are approved therapies in other countries. And to make statements that there is inadequate evidence is ridiculous. The reason there is inadequate evidence is because the FDA has not permitted us to do anything but Phase I studies.”

Until more advanced studies are conducted and new stem cell therapies approved, the treatment that appears to have worked so well on Sara Bomar will not be widely available for patients who suffer from arachnoiditis. Dr. Tennant estimates as many as one million Americans may have the disease, many of them misdiagnosed with “failed back syndrome” or other spinal problems.

“It certainly helped me,” Bomar says of stem cell therapy. “As far as I’m aware, there is nothing else out there could provide this kind of relief.”

Don’t Let Them Stop the Stem Cell Movement

By A. Rahman Ford, Columnist

Somewhat lost in Donald Trump’s presidential victory was the resounding statement made by voters that medical marijuana is here to stay.  Those people-driven victories were monumental for millions suffering from painful and debilitating illnesses -- people who could achieve a life-saving benefit from marijuana or its derivatives. 

It’s only a matter of time before the DEA changes its ridiculous classification of marijuana as a Schedule I controlled substance. 

I believe that one of the next challenges in the wellness movement is the FDA’s control over your own stem cells, or as I call them, personal stem cells.  Quite frankly, the DEA’s position on marijuana is about as misplaced as the FDA’s position on you using the cells God gave you to heal yourself. 

Some scientists have been pushing quite a bit of manufactured controversy around the issue.  Those same scientists tried the same thing with marijuana.  But now the people know the truth.

Personal stem cells are simple to understand.  I’m not talking about embryos, umbilical cords or artificial cells grown by some scientist in a lab.  When I talk about personal stem cells, I’m talking about master cells cultivated from your own bone marrow or fat. 

Yes, you have stem cells in your own body that can heal you.  

In marijuana terms, it’s like you’re your own stem cell “grow house.”  Your own cells can be used to heal any number of physical ailments, including orthopedic issues.  Orthopedists have been using the procedure for years, and there is also evidence that stem cells can be used to heal autoimmune diseases. 

Like marijuana, we really have no idea how many ailments can be improved or even cured with personal stem cells.

If you’re wondering whether personal stem cells can actually heal, look no further than professional sports.  Recently, Bartolo Colon, currently the oldest major league baseball player at 43 years of age, signed a $12.5 million pitching contract with the Atlanta Braves.  How in the world is he able to be so productive at an age where most players are long retired?  You guessed it – his own stem cells.

What about NFL Hall of Famer and two-time Super Bowl winner Peyton Manning, who literally broke his neck playing the game he loved?  Yes, his own stem cells.  International athletes like tennis champion Rafael Nadal have benefitted as well.  In fact, hundreds of professional athletes have healed from serious injuries by using their own stem cells. 

Personal stem cells can work.

Unfortunately, many athletes have to go overseas to use their own God-given healing potential, because the FDA doesn’t allow certain techniques to expand your really strong (mesenchymal) stem cells.  But these wealthy, well-connected athletes who earn their living by being fit -- often enduring severe injuries and pain -- know the truth.  Your own stem cells can heal you.

Just think how many wounded combat veterans could benefit from their own cells!  A 2014 University of Michigan study found that 60 percent of U.S. Army soldiers who were unable to return to a military career after an Iraq deployment couldn’t do so because of a muscle, bone or joint injury. The strongest predictors of inability to serve were fractures and chronic knee, shoulder, spine and back pain. 

But it’s not just musculoskeletal conditions.  Our troops also have crippling brain injuries from IED and other bomb blasts.  According to the Pittsburgh Tribune Review, tens of thousands of combat veterans returning from Iraq and Afghanistan with undiagnosed brain injuries often were ‘thrown into a canyon’ – falling deeper into despair and sometimes flirting with suicide or addiction.”

It gets worse.  To cope with the pain and depression of injury, many wounded warriors turn to addictive pharmaceutical painkillers or illegal street drugs.  A 2011 American Public Health Association report found that the overdose rate for veterans on opioid painkillers was twice the national average, and that they are more likely to become addicted to heroin. 

Opioid abuse is such an epidemic that, in a recent letter to physicians, the Surgeon General called it a crisis and launched the “Turn the Tide” campaign to raise awareness about the issue. 

Fortunately, many wounded warriors have already begun turning the tide by replacing their toxic pills with medical marijuana.  Now, we owe it to our troops to help them turn the tide even further, by giving them another option – personal stem cells.

We celebrate our troops with parades and salutes on Veteran’s Day, Memorial Day and during just about every major sporting event, and justifiably so.  But maybe the best way to celebrate them is to allow them to heal themselves with their own cells so that they can once again be the parents, siblings and children we love.  Our government has a moral and ethical obligation to do so, and we the people have an ethical and moral obligation to make them do it.

Stem Cell Therapy Not FDA Approved

I want to be clear: clinical use of adult, embryonic and umbilical cord stem cells are not FDA approved, and any determination as to their safety or efficacy requires further research (although, in the interest of full disclosure, I have had umbilical cord stem cells in China and the therapy helped me greatly with no negative effects). These stem cells are properly under the domain of the FDA because they are biological agents that are taken from one person and injected into another person and intended to treat a disease. 

What I’m talking about are cells that go from YOU into YOU.  Personal stem cells are as natural as marijuana, and the federal government should acknowledge that your use of your own cells should be a transaction between you and a licensed physician, and regulated at the state level.

States like Colorado and Washington have already proven how safe and healing – not to mention lucrative – marijuana can be, despite what all of the “experts” were saying.  Your own stem cells are no different.

Right now, personal stem cells are technically legal, but the future regulatory landscape is so uncertain that few physicians offer it and few Americans can afford it.  Rather than expanding access to personal stem cells, the FDA has recently tried to restrict their use.

The proposed action by the FDA is wrong.  Unfortunately, it seems like the agency is refusing to hear the cries of persons with disabilities (like myself) and wounded warriors who come home crippled after serving abroad -- so that the children of federal agency bureaucrats can be safe here at home.

I believe marijuana legalization gives personal stem cell advocates hope.  The legalization movement succeeded despite federal intransigence because of the success of direct democracy. People voted at the state level in referendums, without elected officials operating as self-interested intermediaries. 

Given the important nature of this issue, and the apparent ineffectiveness of federal government lobbying and litigation alone, the personal stem cell movement may need to add a referendum component as well.  It may be difficult, but it can be done. 

Educate yourself, and then educate others.  Human beings are not drugs.  We need to keep it that way.

A. Rahman Ford, PhD, is a lawyer and research professional. He is a graduate of Rutgers University and the Howard University School of Law, where he served as Editor in Chief of the Howard Law Journal. He earned his PhD at the University of Pennsylvania.

Dr. Ford is not affiliated with any stem cell treatment provider. He suffers from chronic inflammation in his digestive tract and is unable to eat solid food.

Pain News Network invites other readers to share their stories with us.  Send them to:  editor@PainNewsNetwork.org.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Stem Cell Therapy: Hope or Hype for Pain Patients?

By Pat Anson, Editor

The testimonials sound so encouraging. Chronic pain from arthritis, neuropathy and degenerative disc disease begins to fade after a single injection of stem cells.

“The next day after a needle went in there, the next morning they felt better. Immediately,” says 93-year old Curtis Larson, who suffered from neuropathic pain in his feet and ankles for nearly a decade.  

"Pain’s all gone. Completely gone,” Larson says in a promotional video hosted on the website of Nervana Stem Cell Centers of Sacramento, California.     

“You don’t have to accept chronic joint pain as a fact of life. There’s still hope even if medications and other treatments haven’t worked for you. Our practitioners can explain to you how stem cell treatments work and whether you can benefit,” the Nervana website states. “Relief may be on its way!”

We’ve written before about experimental stem cell therapy and how injections of cells harvested from a patient’s bone marrow or blood are being used to treat chronic conditions such as low back pain.

Professional athletes such as Kobe Bryant and Peyton Manning have used one stem cell treatment – known as platelet rich plasma therapy -- to recover from nagging injuries and revitalize their careers.

But has stem cell therapy moved beyond the experimental stage? Is it ready for widespread use?

“Published data derived primarily from small, uncontrolled trials plus a few well-controlled, randomized trials have not reliably demonstrated the effectiveness of stem-cell treatments,” wrote FDA commissioner Robert Califf, MD, in a commentary recently published in the New England Journal of Medicine – an article clearly aimed at throwing cold water on some of the hype surrounding stem cell treatment.

Califf and two co-authors said there is simply not enough evidence to support some of the newer stem cell therapies – such as cells harvested from a patient’s body fat (adipose tissue).

“The safety and efficacy of the use of stem cells derived from peripheral blood or bone marrow for hematopoietic reconstitution are well established. Increasingly, however, hematopoietic stem cells and stem cells derived from sources such as adipose tissue are being used to treat multiple orthopedic, neurologic, and other diseases. Often, these cells are being used in practice on the basis of minimal clinical evidence of safety or efficacy, sometimes with the claim that they constitute revolutionary treatments for various conditions,” they wrote.

But the lack of evidence and FDA approval haven’t stopped stem cell clinics from popping up all over the country. Over 570 such clinics now operate nationwide, with over a hundred of them in California alone, according to the Sacramento Bee. Some clinics – such as Nervana Stem Cells – are hosting free seminars for chronic pain patients, publicizing them with advertisements that read, “We want you to start living your life pain free!”

A Sacramento Bee reporter attended one seminar and listened to a former chiropractor who works for Nervana tell the audience that they can lower their pain scores from 8’s and 9’s to “mostly 0’s and 1’s” after 16 weeks of injections. He said the clinic has a 90 percent success rate.

Nervana does not use stems cells derived from bone marrow, blood or body fat, but uses a solution of embryonic stem cells from the “after-birth of healthy babies,” the Bee reported. Costs ranged from $5,000 for a single joint injection to $6,000 for a spinal injection. Stem cell therapy is not usually covered by insurance.

“It’s quite clear that these people are offering treatments that haven’t been tested in clinical trials. It’s a little concerning,” Kevin McCormack, a spokesman for the California Institute of Regenerative Medicine told the Bee.  

“There’s a gray zone where these clinics are operating,” he said. “The FDA needs to address the issue of these clinics and address this slow, onerous approval process for stem cell therapy.”

The FDA’s Califf says the agency is not trying to stifle research into a promising new field of medicine -- it’s just waiting for proof that the treatments work and don’t cause harmful side effects. He cited cases in which stem cell patients developed tumors or went blind after injections.

“Such adverse effects are probably more common than is appreciated, because there is no reporting requirement when these therapies are administered outside clinical investigations,” Califf wrote. “The occurrence of adverse events highlights the need to conduct controlled clinical studies to determine whether these and allogeneic cellular therapies are safe and effective for their intended uses. Without such studies, we will not be able ascertain whether the clinical benefits of such therapies outweigh any potential harms.”

Stem Cell Therapy Could Avoid Joint Replacement

By Pat Anson, Editor

An experimental stem cell treatment that grows new cartilage could someday help millions of arthritis patients avoid joint replacement surgery.

Researchers at Washington University School of Medicine in St. Louis and Cytex Therapeutics in Durham, N.C. have developed a 3-D, biodegradable synthetic scaffold that is molded into the precise shape of a patient’s hip joint.

The scaffold, which is covered with cartilage made from the patient’s own stem cells, is designed to be implanted onto the surface of an arthritic hip.

Resurfacing the hip joint with this “living” tissue could ease arthritis pain, and may delay or even eliminate the need for hip replacement surgery, according to researchers.

Joint replacement surgery is usually performed on the elderly to relieve pain from osteoarthritis, a painful and disabling condition caused by a loss of cartilage and the degradation of joints. Over a million hip and knee joint replacement surgeries are performed annually – a number expected to surpass four million by 2030 due to the aging of the U.S. population. 

WASHINGTON UNIVERSITY IMAGE

WASHINGTON UNIVERSITY IMAGE

“We’ve developed a way to resurface an arthritic joint using a patient’s own stem cells to grow new cartilage, combined with gene therapy to release anti-inflammatory molecules to keep arthritis at bay. Our hope is to prevent, or at least delay, a standard metal and plastic prosthetic joint replacement,” said Farshid Guilak, PhD, a professor of orthopedic surgery at Washington University.

After inserting a gene into the newly grown cartilage and activating it with a drug, researchers say the gene will release anti-inflammatory molecules to fight arthritis.

“When there is inflammation, we can give a patient a simple drug, which activates the gene we’ve implanted, to lower inflammation in the joint,” said Guilak. “We can stop giving the drug at any time, which turns off the gene.”

By adding gene therapy to the stem cell and scaffold technique, Guilak and his colleagues believe it will be possible to coax patients’ joints to fend off arthritis, preserve cartilage, and function better for a longer time.

The 3-D scaffold is built using a weaving pattern that gives the device the structure and properties of normal cartilage. It is made with hundreds of biodegradable fiber bundles that are woven together to create a high-performance fabric that functions like normal cartilage.

“The woven implants are strong enough to withstand loads up to 10 times a patient’s body weight, which is typically what our joints must bear when we exercise,” said Franklin Moutos, PhD, vice president of technology development at Cytex.

Scientists have tested the tissue engineering in cell culture, and some customized implants are being tested in laboratory animals. If all goes well, such devices could be ready for testing in humans in three to five years.

Currently, there are about 30 million Americans who have osteoarthritis. That number includes a growing number of younger patients — ages 40 to 65 — who have limited treatment options.  Doctors are often reluctant to perform hip replacement surgery on patients under age 50 because prosthetic joints typically last for less than 20 years. A second surgery to remove a worn prosthetic can destroy bone and put patients at risk for infection and other complications.

“We envision in the future that this population of younger patients may be ideal candidates for this type of biological joint replacement,” said Bradley Estes, PhD, vice president of research and development at Cytex.

The research findings, which are published in the Proceedings of the National Academy of Sciences, are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging, which are both part of the National Institutes of Health (NIH).

Study Tests Stem Cells for Degenerative Disc Disease

By Pat Anson, Editor

An Australian biotech company is testing a new stem cell treatment for degenerative disc disease.

Mesoblast is enrolling patients in a Phase 3 study to see if a single injection of mesenchymal precursor cells (MPCs) taken from the bone marrow of healthy donors can relieve back pain and improve the mobility of patients with disc disease, which occurs when the cushions between vertebrae wear down because of aging, genetics or injuries.

Millions of MPCs are injected directly into the damaged disc in an outpatient procedure. Previous studies have found that MPCs have anti-inflammatory effects, and help strengthen and improve the stability of damaged discs. The treatment is being developed for patients who have exhausted other options for their back pain.

“Patients with this level of degeneration often try multiple treatments for relief, including pain medication, massage, physical therapy, chiropractic adjustments and acupuncture,” says lead investigator Kee Kim, MD, professor of neurological surgery and co-director of the University of California Davis Spine Center.

“For some of them, nothing seems to help, and we end up operating to remove the degenerated disc and fuse the spine to eliminate motion that may cause increased pain. We want to know if a single dose of this investigational therapy can offer relief without the need for surgery.”

UC Davis is one of 28 sites in the United States and Australia involved in the study. Participants with degenerative disc disease in the lower back will receive injections of either MPCs, MPCs with a carrier material (hyaluronic acid) or a placebo. Although the MPCs are collected from donors, tissue matching is not necessary.

Following treatment, participants will be evaluated by researchers six times over the course of a year. They also will be given the option to participate in an extension of the study to track their progress for three years after the initial injection.

Previous studies have found that MPCs have anti-inflammatory effects, and help strengthen and improve the stability of damaged discs. Researchers caution, however, that the treatment may not be effective for everyone.

“Many patients with back pain will not benefit from this stem cell therapy and may still require surgery,” Kim said. “For some patients, it could offer improvement. For these patients, it is worth exploring this alternative.”

You can find out more about the study by clicking here.

Stem Cell Study for Back Pain Begins

By Pat Anson, Editor

Enrollment has begun in a clinical study of an experimental stem cell therapy that could – if proven successful – revolutionize the treatment of low back pain caused by degenerative disc disease.

About 330 adults with chronic low back pain who have not responded to conventional therapy will be enrolled in the Phase III “Cascade” study at over two dozen medical centers in the United States. Participants will be injected in the lumbar disc with millions of Mesenchymal Precursor Cells (MPCs) – adult stem cells derived from donated bone marrow.

An earlier Phase II study showed that a single injection of a 6 million cell dose of MPCs reduced low back pain and improved function for at least 12 months. Participants also used fewer opioids for pain relief and required less treatment.

“If you look at the study as a whole, people who received the 6 million stem cell injection into the disc, 70 percent of them had a reduction of their pain of 50% or greater. These were clinically relevant changes,” said J. Scott Bainbridge, MD, lead investigator at Denver Back Pain Specialists, one of the clinics participating in the Cascade study.

"The clinical program is the first of its kind in the United States and we are very excited by the potential of these adult stem cells to provide a novel therapeutic approach."

Bainbridge says the stem cell injection takes up to two months to stop the pain and inflammation triggered by degenerative disc disease.

“It takes time for the stems cells to normalize the inflammatory condition,” Bainbridge told Pain News Network. “You’re taking a disc that is on a degenerative cascade or path. The stem cells regulate that, they change it from an inflammatory stage to an anti-inflammatory, homeostatic state. It turns on the engine, if you will, to start building and producing some of the things that will help the disc become hydrated and build back some of its structural integrity.”    

Degenerative disc disease is the most common cause of low back pain, which develops with the gradual loss of proteoglycan, a substance that cushions the bones of the spine and enables normal motion.

Conventional treatment includes pain medication, physical therapy or surgical intervention such as a spinal fusion. Bainbridge says stem cell injections have the potential to become a frontline treatment, to be used before a riskier treatment such as surgery.

The Cascade study is sponsored by Mesoblast Limited, an Australian company focused on cell-based regenerative medicine. Mesoblast is also developing stem cell treatments for rheumatoid arthritis and diabetic neuropathy, using “off-the-shelf” stem cells from healthy adult donors that do not require tissue matching.

“(There) is compelling evidence that Mesoblast’s stem cell technology has the potential to change the treatment of spinal disease from focusing on surgical reconstruction to biologic regeneration. Physicians and patients are seeking access to a new modality to treat patients with this highly debilitating disease for whom there are limited options,” said Hyun Bae, MD, Medical Director at the Cedars-Sinai Spine Center in Los Angeles, which participated in the Phase II study.

Unfortunately, it could take years for the therapy to win approval from the U.S. Food and Drug Administration. The Cascade study alone is expected to take about three years. For further information about the study and a list of the 25 clinics that are recruiting participants, click here.

‘Amazing’ New Stem Cell Treatment for Neuropathy

By Pat Anson, Editor

Researchers at Duke University say an experimental stem cell therapy being tested on animals shows great potential to provide long-lasting pain relief for people suffering from diabetic neuropathy or other types of nerve damage.

In a study published in the Journal of Clinical Investigation, researchers said mice injected with a type of stem cell known as bone marrow stromal cells (BMSCs) were much less sensitive to nerve pain.

"This analgesic effect was amazing," said Ru-Rong Ji, PhD, a professor of anesthesiology and neurobiology in the Duke School of Medicine. "Normally, if you give an analgesic, you see pain relief for a few hours, at most a few days. But with bone marrow stem cells, after a single injection we saw pain relief over four to five weeks."

BMSCs are known to produce an array of healing factors and can be coaxed into forming other types of cells in the body. They are already being used to treat people with serious burns, inflammatory bowel disease, heart damage and stroke.  

"Based on these new results, we have the know-how and we can further engineer and improve the cells to maximize their beneficial effects," said Ji.

Researchers injected the mice with stem cells through a lumbar puncture, infusing them into the fluid that bathes the spinal cord.

The picture on the right shows how the injected stem cells (in red) migrated to the site of the nerve injury and were still present four weeks after treatment.

A molecule emitted from the injured nerve cells -- which has previously been linked to neuropathic pain – is believed to act as a “homing signal” and attract the stem cells.

Researchers measured levels of anti-inflammatory molecules in the mice and found that one in particular, TGF-β1, was present in higher amounts in the spinal fluid of the stem cell-treated animals.

TGF-β1 is a protein that is secreted by immune cells and is common throughout the body. Research has shown that people with chronic pain have too little TGF-β1.

courtesy duke university

courtesy duke university

Injecting TGF-β1 directly into spinal cord fluid provides pain relief, but only for a few hours, according to Ji. By contrast, bone marrow stromal cells stay on site for as much as three months after the infusion.

Ji’s research team is working to identify stem cells that produce more TGF-β1, as well as other types of pain relieving molecules. In addition to diabetic neuropathy, researchers believe stem cell therapy could also be used to treat pain from chemotherapy, surgical amputation, lower back pain and spinal cord injuries.

Nearly 26 million people in the United States have diabetes and about half have some form of neuropathy, according to the American Diabetes Association.  Diabetic peripheral neuropathy causes nerves to send out abnormal signals. Patients feel pain or loss of feeling in their toes, feet, legs, hands and arms. It may also include a persistent burning, tingling or prickling sensation. The condition can lead to injuries, chronic foot ulcers and even amputations.

Another recent animal study by researchers in the U.S. and South Korea found that diabetic rats given intramuscular injections of bone marrow stromal cells experienced both angiogenesis (blood vessel growth) and a restoration of the myelin sheath -- a protective covering over nerve cells damaged by neuropathy.

"Currently, the only treatment options available for DN (diabetic neuropathy) are palliative in nature, or are directed at slowing the progression of the disease by tightly controlling blood sugar levels," said Dr. John Sladek, Jr., Professor of Neurology, Pediatrics, and Neuroscience, Department of Neurology at the University of Colorado School of Medicine.

"This study offers new insight into the benefits of cell therapy as a possible treatment option for a disease that significantly diminishes quality of life for diabetic patients.”

The study is being published in the journal Cell Transplantation.