DUBLIN – The global market for unproven cell therapies may be worth as much as $2.4 billion, according to a report published Thursday by the International Society for Cellular Therapy (ISCT).

The report estimated that about 60,000 patients are receiving such treatments every year, paying up to $40,000 each for therapies that have little if any underlying scientific rationale, no supporting preclinical or clinical data and are often produced according to dubious manufacturing procedures. In addition to the very real risk of physical harm to patients, the problem could also undermine the emergence of legitimate cell therapies that could actually offer patients real treatment options in the future.

“We’re really concerned about it,” Kurt Gunter, who was the ISCT’s president until last year and who was one of the 23-person team that produced the report, told BioWorld Today. “If you think about it, taking advantage of patients is something that’s been going on for decades, if not for centuries.”

Although the problem may never be eliminated, he said, it can be managed more successfully than is the case at present. The ISCT is embarking on a campaign, to which it aims to attract a broad array of stakeholders, including patient groups, professional societies and regulatory authorities, in order to develop a globally harmonized approach. Included in its recommendations are the establishment of a publicly accessible safety registry and the provision of tools to patients to enable them to evaluate potential treatments. “We want patients to be able to make their own decisions,” said Gunter. “This is a whole continuum of risk.”

There are initiatives already under way that embody a similar ethos. ALSUntangled, for example, offers patients with amyotrophic lateral sclerosis (ALS) concise, authoritative scientific and clinical assessments of off-label therapies – which are nominated by the patients themselves.

A GLOBAL PROBLEM

The ISCT report does not detail specific instances of dubious practices, but the list of shady exemplars is lengthening. “For every one that makes the press, there are several others that don’t get reported,” Gunter said.

The Oct. 5, 2015, issue of the CDC’s Morbidity and Mortality Weekly bulletin details an outbreak of Q fever among five residents of New York state, plus one Canadian, all of whom had traveled to Germany last year to receive intramuscular injections of fetal sheep cells in order to “improve their general health and vitality.” Three of them had pre-existing medical conditions – one had atrial fibrillation with kidney stones, another had multiple sclerosis and a third had Parkinson’s disease.

All six tested seropositive for Coxiella burnetii, the intracellular bacterial pathogen that causes Q fever, and they experienced symptoms including fatigue, chills, sweats and sleeping difficulties. The symptoms have continued for more than nine months in three of the patients.

The most notorious recent example of the dangers of unproven cell therapy also comes from Germany. In 2010, an 18-month-old boy from Romania died after receiving an injection of stem cells directly into the brain at the XCell-Center, which ran clinics in Cologne and Dusseldorf. It exploited a loophole in Germany’s regulations, which enabled it to continue treating patients with a wide range of neurodegenerative conditions and other chronic diseases with a stem cell protocol for which it had published no supporting data. It was shut down by the authorities in 2011, when changes in Germany’s legal regime came into effect.

“I don’t think it’s fair to pick on Germany. This is a global problem,” Gunter said. Indeed, the individual behind XCell-Center, a Dutch doctor called Cornelis Kleinbloesem, has resurfaced in another venture, Cells4Health Therapeutics Ltd. According to its website, its current address is in Sofia, Bulgaria, although earlier media reports had traced it to Lebanon. That venture had previously operated in the Netherlands until its closure in 2006.

A web-based analysis, cited in a recent New England Journal of Medicine perspective article, titled “Medicine’s Wild West — Unlicensed Stem-Cell Clinics in the United States,” argues that, adjusted for population, the U.S. has more unlicensed clinics marketing unproven cell therapies than any other country. Those exploit the vagueness of Section 361 of the Public Health Service (PHS) Act, which does not expressly rule out the use of “minimally manipulated” human cells, tissues, and cellular and tissue-based products (HCT/Ps) in medical practice. The FDA, however, may be about to tighten up its definitions. In December 2014, it issued draft guidance on regulatory considerations underpinning the derivation of HCT/Ps from adipose tissue. The adipose-derived stromal vascular fraction, obtained during liposuction procedures, is used widely in unproven stem cell therapies.

The ISCT, which is based in Vancouver, British Columbia, has 1,300 members, who include academic and industry-based scientists and clinicians. The report is available online and will also appear in the January 2016 issue of the society’s journal Cytotherapy.

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