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Stem Cell Reality: Desperate patients are vulnerable to the promise of stem cell therapy—most of it unproven. Protect your health—and your wallet—with these facts.

Shaw, Gina

doi: 10.1097/01.NNN.0000511240.42939.e8
Departments: New Frontiers

A stroke in 2009 left Jim Gass, now 66, with a paralyzed left arm and a weakened left leg. He could still live independently in his home in Wilmington, MA, half an hour north of Boston, but he needed a leg brace and a cane to walk—a depressing setback from his previously vigorous life. Seeking improvement, he scoured the internet, finding hopeful anecdotes touting the promise of stem cell therapy to treat everything from multiple sclerosis (MS) and Parkinson's disease to traumatic brain injury and stroke.

Over the next several years, Mr. Gass told The New York Times, he spent nearly $300,000 on treatments at unregulated clinics in Mexico, China, and Argentina—places with glowing testimonials from former patients who claimed miraculous cures. His doctors and family members strongly discouraged him, but Mr. Gass couldn't be dissuaded. He was willing to spend whatever it took to get back what he'd lost. The worst that could happen, he figured, was that he wouldn't get any better. He was wrong.

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MYSTERIOUS GROWTH

Gass had first sought stem cell treatments in China and Argentina in 2011. They didn't seem to help much, but they didn't hurt, either, so he tried again. In 2014, he went to Mexico, where fetal stem cells from Russia were injected into his spinal cord. At first, Gass thought his walking had improved—but then he started to notice pain when he was lying down. He began to fall frequently. He underwent an MRI scan of his spine at Brigham and Women's Hospital, where doctors discovered an enormous mass pressing against the lower portion of his spinal column.

SCAMMED

SCAMMED

It turned out that the mysterious mass wasn't quite a cancer, but it wasn't benign, either. In an article in the New England Journal of Medicine, doctors wrote, “It could not be assigned to any category of previously described human neoplasm [an abnormal growth] on the basis of the data we gathered.” But one thing was certain: the mass was partly made up of cells from another human being and had originated with the stem cells.

Radiation treatments initially shrank the mass and gave Gass back some of the mobility he'd lost, but in the spring of 2016 another scan showed that the mass had begun to grow again. The former lawyer is now paralyzed from the neck down, except for his right arm. He has relocated to California, where he is working with a paralysis recovery center in San Diego County. Doctors are stumped and have no idea how to stop the tumor from growing.

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THE ORIGINS OF STEM CELL THERAPY

Stem cell therapy has been around since at least the mid-1960s, when researchers first started transplanting bone marrow (or hematopoietic cells) to treat cancer, blood diseases, and disorders of the immune system. More recently, stem cells have also been used in tissue grafts to repair injuries or for diseases of the skin, eyes (specifically the corneas), and certain musculoskeletal tissues, including bone and cartilage. These are the only conditions for which stem cell therapy has been approved by the US Food and Drug Administration (FDA). All other uses of stem cells in medical treatment, including in neurologic diseases, are unproven and experimental at this point.

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WHAT ARE STEM CELLS?

Every organ and tissue in the human body has its origins in stem cells, which have two special characteristics. First, they can make copies of themselves. Second, when they divide, instead of just replicating themselves, they can turn into another type of cell in the body.

Different types of stem cells have distinct abilities. Human embryonic stem cells are derived from the inner cell mass of the blastocyst, a group of cells that form a few days after a sperm fertilizes an egg. They can develop into every cell type in the body, which defines them as being pluripotent. Adult stem cells are tissue-specific, meaning that they can only develop into cells for the tissue or organ from which they were extracted, such as skin, muscle, or bone marrow.

The blood-forming hematopoietic stem cells are the most understood. They can turn into red or white blood cells, or platelets, and have been particularly effective in treating blood-borne cancers such as leukemia, Hodgkin's lymphoma, and multiple myeloma.

Another type, induced pluripotent stem cells, or iPS cells, are created in a laboratory. Scientists have found ways to genetically reprogram adult stem cells into cells that act more like embryonic stem cells. They are useful for studying diseases and testing new therapies.

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THE PROMISE OF STEM CELLS

Researchers are particularly focused on investigating cell-based therapies, using stem cells to replace or repair damaged organs and tissues. In the future, it may be possible to regenerate damaged heart muscle, repair an injured spinal cord, or replace missing or injured neurons in the brains of people with Parkinson's disease or Alzheimer's disease. Scientists are even working on ways to grow entirely new organs from stem cells. Still, despite the potential of these experimental approaches, therapies are years away from being proven safe and effective.

Unfortunately, that hasn't stopped the proliferation of clinics in the United States and abroad offering stem cell therapy for all kinds of neurologic diseases. Nor has it stopped people like Gass from shelling out thousands of dollars for these so-called treatments, says Gary Gronseth, MD, FAAN, professor and vice chair of neurology at the University of Kansas.

People with neurologic conditions are particularly vulnerable to unscrupulous claims because so many neurologic disorders are progressive and existing treatments can't alter the course of the disease. “Consider people with amyotrophic lateral sclerosis (ALS), a disease that's relentlessly progressive and fatal,” says Dr. Gronseth. “These patients and their families are desperate to try new therapies, even ones that are unproven, just in the hope that maybe this one will turn out to be legitimate.”

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DESPERATE FOR HELP

The journey to stem cell treatment often starts with an anecdote from someone who claims to have been cured by the procedure, either heard in person or found on the internet, or both. That's what happened to Gass—he had read accounts online—and to Joe and Nettie Aufenkamp.

The Aufenkamps first heard about stem cell therapy from a flight attendant on a trip to Las Vegas. “She had been paralyzed after a car accident and told us that she had gone to Germany for a stem cell transplant, with excellent results,” recalls Nettie. Like the flight attendant, Joe had been in a car accident: An out-of-control semi-tractor trailer had spun into his car and sent it flying into a ditch. Joe, who was 48 at the time, sustained head trauma and spent weeks in a coma. After emerging from the coma, he had balance and coordination problems, extreme weakness, and short-term memory loss.

For more than a decade, he and Nettie had looked for any possible treatment that could improve his condition. He underwent extensive physical therapy but was still unable to walk without a walker. And his speech, which had been compromised since childhood by cerebral palsy, worsened after the accident, and no amount of speech therapy made a difference.

After hearing about the flight attendant's experience, the Aufenkamps searched the internet for information about stem cell therapy for traumatic brain injury. They eventually found a clinic in Arizona. The clinic's website states that none of its treatments are approved by the FDA, but it also says that “many reputable international medical clinics” use stem cell therapy to treat chronic degenerative conditions, including neurologic diseases. The website also explained that it harvests stem cells by removing a small sample of fat tissue from a patient's lower back or abdomen. Then those cells are injected back into the patient, either into the skin or muscle near the affected area, or are administered through a nasal spray.

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UNVERIFIABLE TREATMENT

“They sent us references, and we decided to go for it,” says Nettie, even though her husband's doctors opposed the treatment. Joe and Nettie plunked down $7,000 in cash and signed consent forms saying they wouldn't file with insurance or sue if anything went wrong.

The Aufenkamps were told the only risk of the procedure was possible infection in the area where the cells were extracted. Infection is usually the greatest concern with most injections of stem cells, but it's not the only hazard, says Nicholas Maragakis, MD, director of the Michael S. and Karen G. Ansari ALS Center for Cell Therapy and Regeneration Research at Johns Hopkins University in Baltimore. “There is also potential for bleeding, and any time you deliver stem cells to any region, there is potential for them to malignantly transform into a tumor. No one should undergo a procedure like this outside of a well-controlled clinical trial at a reputable research institution.”

Joe received a nasal spray, which was purportedly administered to open up the sinus cavity. Then he had to sniff deeply for a count of three to bring the cells in deeper. “It was explained that the cells would attach throughout the sinuses and brain and cascade downward,” Nettie says.

For the first 48 hours after the nasal spray, Joe's speech was clear and fluent, says Nettie, but it didn't last. Once they returned home, they noticed another improvement: Joe seemed to be able to stand more independently. “We have a power chair with a lift that comes out of the back of our van, and he was able to stand there without hanging onto anything and loosen the straps,” Nettie says. That improvement also faded, and today Joe copes with all the same day-to-day impairments he had before getting the stem cell treatment.

Misunderstanding of the placebo effect or of the natural history of recovery or progression of certain illnesses or injuries makes it easier for unscrupulous stem cell clinics to sell their snake oil, explains Clive Svendsen, PhD, the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine at Cedars-Sinai Medical Center in Los Angeles. “There would need to be a double-blind, placebo-controlled trial to demonstrate the ability of a spray like this to provide temporary relief of symptoms. So far, no such trials have been conducted. I think this family's experience is typical of what many people who seek unproven stem cell treatments report: mild placebo effect followed by no lasting change. They feel better for having tried, but they are also $7,000 worse off, and the clinic has sold them a scam treatment.”

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INEFFECTIVE, EXPENSIVE, AND UNSAFE

And as Jim Gass' story illustrates, the outcomes for people who seek these treatments can be much worse.

Although stem cell therapy holds great promise, many unknowns remain. That is why the treatment must be administered and monitored closely in clinical trials. “When cells are taken from fetal tissue and the tissue hasn't been processed correctly, that can be very dangerous,” says Dr. Svendsen. “Because these cells can renew themselves infinitely, they have the potential to replicate out of control and cause tumor growth.”

Dr. Maragakis says almost every one of his patients asks about stem cell therapies. “I've talked with people who had their bone marrow cells isolated and injected back into their bodies, with the claims of magical stabilization of disease after one day, only for the patients to return to their previous condition after a few days,” he says. “In China, people were getting cell transplants right into the brain itself.”

With such clinics springing up around the world and defying regulatory efforts to close them, more and more people will likely be ensnared—and risk disastrous outcomes like what Jim Gass experienced.

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PIPELINE PROJECTS

In the meantime, legitimate research continues. Various types of stem cells are being studied for many neurologic conditions in test tubes or on animals. A few approved clinical trials are underway to test stem cell treatments for conditions such as ALS, spinal cord injury, and stroke, with more on the horizon.

FDA-approved clinical trials in a number of stroke centers are now researching the effectiveness of mesenchymal stem cells—a specific type of adult stem cell usually found in bone marrow or connective tissue—in reducing inflammation and helping the brain repair itself after stroke. These cells do not survive more than two weeks in the body and would probably be used more like a drug that would have to be given at regular intervals, Dr. Svendsen explains.

A few human clinical trials are testing various methods for spurring stem cells to take root and grow within the brain and central nervous system. As of press time, three companies are approved by the FDA to conduct clinical studies using direct injections of neural stem cells. [See “3 Neural Stem Cell Studies” below.]

Dr. Svendsen's group at Cedars-Sinai is awaiting FDA approval for clinical trials using a combination of stem cells and gene therapy in another ALS trial. They have developed fetal tissue cells engineered to make a substance called glial cell line-derived neurotrophic factor (GDNF), which has been found to protect motor neurons from damage in animal models of ALS, but not yet in human trials.

“We modify human neural stem cells to produce GDNF and then inject them directly into the spinal cord. There they act as Trojan horses, arriving at sick motor neurons and delivering the growth factor exactly where it is needed,” he explains. The researchers are testing the safety of this approach in a phase 1 trial.

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SIGN UP FOR LEGITIMATE TRIALS

To participate in an approved clinical trial of stem cell therapy, search http://clinicaltrials.gov to find studies that might be right for you. No legitimate clinical trial should ever require that you pay for the treatment you receive. If you choose to enroll in a trial, you might benefit from a new therapy if you receive it, says Dr. Gronseth. “You're also contributing to medical science by helping to figure out whether a new therapy actually works.”

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IRRESISTIBLE PULL

With just a few legitimate trials currently available, Dr. Maragakis understands that patients who have no other options for stopping or reversing the course of their disease can be tempted by the unproven promises of stem cell clinics. “I discuss the risks and the costs of these places with my patients. I tell them how rigorous the science has been to get legitimate research to the point it is now,” he says. “But I also tell them I will support whatever decision they might make. The reality is, though, that none of my patients who have tried these treatments have come back thinking that it helped them. Most often they tell me, ‘For the first week or two, I felt like it was helping, but now things are just the same as they were before.’”

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Protect Yourself from Stem Cell Scams

Despite a government crackdown, the number of clinics offering unproven treatments continues to rise. In September, the US Food and Drug Administration held a two-day public meeting focused on regulation of human cells, tissues, and cellular- and tissue-based products.

Until federal and state regulations are enforced more aggressively, you can avoid enrolling in bogus trials by asking these questions:

  • Is this treatment based on a randomized, controlled trial in which patients given the stem cell therapy were compared to similar patients not treated with stem cell therapy? Individual patient testimonials may be impressive, but they're not scientific evidence.
  • How many people were in the trial? In smaller trials, it's harder to distinguish between a true treatment effect and random variation.
  • Were the results assessed by “blinding,” meaning the researchers determining whether or not a patient improved did not know which patient received stem cell therapy and which did not? Blinding prevents the findings from being manipulated, intentionally or unintentionally.
  • How many patients with my condition experienced permanent improvement after the therapy? Be wary of dramatic claims that the treatment has cured or brought major improvements to most patients.
  • What diseases can be treated with this therapy? If the response is a long list of varying conditions, be skeptical.
  • How does this treatment actually work? Consider whether the answer seems to make sense. For example, how would cells taken from your own fatty tissue migrate, take root in the brain, and form new brain cells?
  • Where are the cells coming from? “Push them on that, and get it in writing,” says Clive Svendsen, PhD, the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine at Cedars-Sinai Medical Center in Los Angeles. He strongly advises avoiding any centers that claim to administer fetal tissue-derived stem cells outside of a clinical trial.

For example, he points to one stem cell clinic, Stem Cell of America in California, that claims to have used fetal-derived cells to “successfully treat” everything from Alzheimer's disease to stroke in more than 3,000 patients, with no known negative side effects. “That's pretty much every red flag there is, and every claim you would expect from people who are making money from this,” he says.

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3 Neural Stem Cell Studies

Three companies have received FDA approval to start trials using neural stem cells for neurologic conditions

Neural stem cells AXOL BIOSCIENCE LTD

Neural stem cells AXOL BIOSCIENCE LTD

  • Neuralstem, Inc. This biotech company in Rockville, MD, has completed a phase 2 trial (which tests for efficacy) in amyotrophic lateral sclerosis (ALS) in which human spinal cord-derived stem cells were injected directly into the spinal cord to protect the motor neurons that are destroyed by the disease. Results from the trial have not yet been published. The company announced in mid-2015 that the treatment appeared to be safe and well tolerated, and early findings showed that 47 percent of patients had some response to the therapy, either improving or showing almost no decline on functional status tests.
  • ReNeuron This UK-based company has phase 1 trials (which test the safety of a procedure) and phase 2 trials (which test for efficacy) underway in stroke. Neural stem cells are injected directly into the brain, where it's thought that they may reduce inflammation and release growth factors that help rebuild damaged areas.
  • Q Therapeutics, Inc. Based in Salt Lake City, UT, this company received approval last year to begin a trial of its patented glial progenitor cells into the spinal cords of people with ALS. The company hopes the cells will combat the disease by successfully developing into two different types of specialized cells that protect neurons and improve transmission of nerve signals in the brain and spinal cord. The trial is still in the planning stages.

To find out more about these and any future trials of stem cell therapies, search http://clinicaltrials.gov for “stem cell” and the condition you're interested in.

© 2016 American Academy of Neurology