Adding year-end urgency to the national debate over stem cells, a prominent UC Davis researcher is asking federal officials to send warning letters to hundreds of stem cell clinics nationwide that he contends are selling patients risky, unproven therapies.
Citing uncertainty over how the incoming Trump administration will handle stem cell use, professor Paul Knoepfler, a stem cell researcher at the UC Davis Medical School, said “now is the time” for the U.S. Food and Drug Administration to finalize guidelines and send notices to clinics that are offering untested treatments.
“There’s a closing window of time, prior to the (Donald) Trump inauguration, when the FDA could take action and have a positive impact by reining things in that have gotten out of control,” said Knoepfler. “These clinics are operating outside the normal scope of FDA oversight.”
His appeal was posted Sunday in an open letter to FDA officials on his stem cell blog, The Niche.
It comes as stem cell clinics have proliferated nationwide, promising relief for everything from autism to cancer. Earlier this year, Knoepfler and a University of Minnesota colleague identified 570 stem cell clinics nationwide that were advertising non-FDA-approved treatments for varied ailments. Of those, about 113 are in California, including Nervana Stem Cell Centers in Fair Oaks and San Diego.
Stem cells, which have the ability to regenerate and repair damaged tissue inside humans, hold enormous appeal and potential, both to researchers and the public. But regulations in how they’re used are somewhat murky. The FDA has issued draft guidelines, hosted two public hearings and written in medical journals about its concerns over misuse of nonapproved stem cell treatments.
But it is in no hurry to issue final guidelines, FDA spokeswoman Andrea Fischer said this week in an email.
“This is an important topic and the FDA is still evaluating the feedback we received as we work to finalize our guidance, which is intended to provide clarity” over the use of human cell, blood and tissue products, Fischer said. “While we hope to issue finalized versions promptly, we are not able to speculate on when that will be.”
If a stem cell clinic has questions about how to proceed, she added, “we encourage them to reach out to FDA to discuss.”
A spokesman for the California Institute for Regenerative Medicine, the state’s voter-approved stem cell research center, said he can’t comment specifically on Knoepfler’s call for FDA action, but supports “any approach that protects patient safety.”
“We have been concerned for many years about the proliferation of clinics offering unproven, unregulated therapies and claiming they can cure everything from arthritis to Alzheimer’s,” said institute spokesman Kevin McCormack in an email. In the last 10 years, the institute has allocated about $2.4 billion to academic institutions and private companies for stem cell research and clinical trials.
Under FDA guidelines, stem cells that are “minimally manipulated” (they aren’t changed much) and used homologously (in roughly the same place in the recipient’s body as in the donor’s) are not considered a drug and don’t require strict FDA approval.
But that leaves open questions about how different clinics handle stem cells, where they’re obtained, if they are safe and whether they show verifiable benefits when injected into patients for varied ailments and diseases.
Last month, seeking to clarify the agency’s stance, top FDA officials said that while they “share the excitement” of potential benefits from stem cell therapies to improve chronic conditions or certain diseases, those promises can’t be assured without scientific proof.
In most cases, the notion that stem cells are “intrinsically able to sense the environment into which they are introduced and address whatever functions require replacement or repair – whether injured knee cartilage or a neurologic deficit – is not based on scientific evidence,” said FDA Commissioner Robert Califf and two top researchers, writing last month in the New England Journal of Medicine. “This lack of evidence is worrisome.”
They cited instances where stem cells injected into patients’ eyes to treat macular degeneration resulted in worsened vision, even blindness. In another case, they said, a patient treated for kidney disease developed stem cell-caused tumors.
Other reports of tumors and abnormal growths have been cited in recent years, particularly in cases of “stem cell tourism,” where patients have traveled for treatment to clinics in Argentina, China, Mexico and elsewhere.
Such harmful outcomes, the FDA officials noted, may be even more common, since there is no reporting requirement of adverse results in nonclinical-trial settings.
At the same time, they sought to refute critics who say the federal approval process is too cumbersome and costly, thereby denying patients therapeutic care they desperately need. Califf and his colleagues, for instance, said stem cell treatments that “truly provide an impressive benefit” to patients could be statistically shown to be beneficial in randomized trials with as few as 42 participants.
For stem cell doctors, the proof is in their patients.
Dr. Robert Ghelfi, a general surgeon in Redding who began offering stem cell treatments for arthritis pain and chronic heart disease about two years ago, said stem cells aren’t a panacea for all ailments but in carefully controlled situations can help patients with few other options.
“People have unreasonable expectations of what stem cells can do. I don’t think it’s magic but in the right situation, (stem cells) can make people’s lives better. … When they come in with an 8 of 10 on a pain scale, if we can get them down to 4 or 5, that to me is successful. ”
Ghelfi, who runs the Northern California Stem Cell Treatment Center, said he turns down about 75 percent of patients who ask for treatment. “If you’ve got a torn ACL, you probably should have surgery. But if you’re an 85-year-old woman with a bad knee, surgery may be risky or you’re afraid of it. … There are certain conditions where (stem cells) can make a difference in people and ease their pain levels.”
He uses “adipose-derived” stem cells taken from the patient’s own fat layers. With a “mini-liposuction” technique, Ghelfi extracts fat tissue, usually from the patient’s abdomen or flank, then spins it to concentrate millions of stem cells, which are injected directly into the affected area of the patient’s body.
“We’re not growing stem cells, we’re not manipulating them,” said Ghelfi, who’s done about 220 injections in the last two years, primarily in patients with arthritic pain in their knee, back, neck or fingers, as well as those with chronic obstructive pulmonary disease. He charges about $6,000 to $7,000 per injection but said it’s rare that patients need more than one. As part of a national network of stem cell physicians, Ghelfi said, he follows strict federal treatment protocols and does three-month followups with patients to check on their condition.
Earlier this month, President Obama signed the 21st Century Cures Act, a broad-ranging medical funding bill that includes language to allow faster FDA approval of certain stem cell therapies. But how those changes get implemented remains unclear.
UC Davis’ Knoepfler said his biggest concern is patients who may be paying too high a price. While many stem cell clinic websites state that their therapies do not have FDA approval, patients may be unknowingly exposed to both health and financial risks, he said. The non-approved treatments are not covered by insurance.
“I worry about a person scraping together money for something that’s not proven. Are they really getting anything out of it?” Knoepfler asked. “I don’t know if they really know it’s an experiment and what happens if something doesn’t go quite right.”
Knoepfler said he worries that the incoming administration may be less interested in regulatory oversight. As part of his first 100-days action plan, President-elect Donald Trump said he is “cutting the red tape” and intends to speed up the FDA’s regulatory approval of life-saving medications.
“There may be an inclination to have less strict requirements for patients receiving experimental therapies,” said Knoepfler. “That may or may not impact the FDA’s oversight of stem cells. But it’s something to keep in mind.”