The Low-Down on Stem Cell Tourism for Neurological Diseases

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Starting in August 2017, the FDA began cracking down on unscrupulous organizations peddling bogus or unproven-and in some cases dangerous-stem cell treatments. So far, the FDA has taken steps in Florida and California against what it termed “troubling products.” The agency has also formed a working group to “pursue clinics through whatever legally enforceable means are necessary to protect the public health.”¹

In May 2018, the FDA sought permanent injunctions against two stem cell clinics, Sunrise Stem Cell Clinic LLC in Florida and California Stem Cell Treatment Center Inc in California, for marketing products without FDA approval and engaging in serious infractions of good manufacturing practice requirements.²

In particular, California Stem Cell Treatment Center was selling products claiming to treat a variety of medical disorders, including neurological conditions like stroke, Parkinson Disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). The center is not alone in targeting debilitating or terminal neurological conditions. These conditions tend to be a favorite area for clinics peddling false hope to patients who are vulnerable, desperately searching for a cure, and often willing to pay large sums of money for procedures not covered by insurance. 

Some have traveled overseas for treatments that may cost up to $80,000, not including the costs of travel. An estimated 700 stem cell clinics are located in 37 international locations, mostly in Asia, Europe, Central America, and the Caribbean. The top three conditions marketed by such clinics are MS, PD, and stroke.

But stem cell tourism is also a domestic problem. At least 570 clinics in the US offer unproven stem cell therapies. The largest number of clinics are found in California, Florida, Texas, Colorado, Arizona and New York. Eighty of these businesses market treatments for neurological diseases, including MS, ALS, PD, AD, spinal cord injury, stroke, and “neuralgia.”

Most clinics acknowledge that their treatments are not FDA approved. Many use cells from subcutaneous fat tissue, and claim that these may represent mesenchymal stem cells or immune cells.

Such treatments are not without risk. A recent review of safety incidents following use of unproven stem cell treatments and reported in PubMed and Google, found 35 reported cases of serious complications following stem cell treatments, 10 of which resulted in death and 18 of which were done for neurological conditions. Many of the serious complications were devastating inflammation of the CNS. Patients who suffered adverse events or died were treated at clinics in 14 countries. However, the review was limited because it relied on reported cases, while the true number of cases is likely to be much higher.⁵

The specter of bogus treatments undermines legitimate research in stem cell technology. A good example is research going back at least 20 years on autologous hematopoetic stem cell transplantation (aHSCT) in the treatment of aggressive MS. Since 1997, over 1000 patients with MS have been treated with aHSCT and reported to the EBMT Registry, the largest stem cell registry in Europe.⁵

aHSCT is thought to work through an anti-inflammatory effect. Treatment consists of destroying autoreactive cells in the bone marrow followed by transplant and extensive renewal of the immune system.⁵

While aHSCT for aggressive MS has not yet gained FDA approval, a recent meta-analysis of all published studies since 1995-2016 (15 studies covering 764 transplant patients), provided support for research suggesting that patients with aggressive, relapsing-remitting MS have a better benefit-to-harm ratio than those with progressive disease.⁶

The benefit-to-harm ratio is an important consideration. aHSCT carries serious risks, including transplant-related mortality, mostly due to infections related to immunosuppression, cardiotoxicity, veno-occlusive disease, neurological deterioration, and liver failure. In recent years. improved selection of patients as well as accumulating experience in transplant centers may have contributed to a drop in transplant-related mortality.⁵

RCTs are ongoing or planned, but most are in phase I or II. The MIST trial is comparing aHSCT with FDA approved standard of care, and is being conducted in the US, Sweden, and England, with an estimated completion date of December 2018. At NYU, an FDA-approved, Phase II double blind placebo controlled RCT is currently recruiting, and will investigate autologous mesenchymal stem cell transplant in progressive MS.

Other trials in development include: the NIH-supported BEAT-MS trial in the US, the NET-MS trial in Italy, the RAM-MS trial in Denmark, Norway and Sweden, and the STAR-MS trial in the UK.⁵

While waiting for legitimate research to progress, states and countries are enacting laws and creating regulating bodies to crack down on disreputable players in the stem cell field. The International Society for Stem Cell Research (ISSCR) has created a web site with information for patients about stem cell treatments (www.closerlookatstemcells.org). And experts are calling for a national registry of stem cell tourism complication, in order to get a better handle on the extent of the problem.

Take home points
• The FDA is cracking down on disreputable clinics offering unproven stem cell therapies
• Stem cell tourism is a global problem, often with an emphasis on neurological conditions; treatments have resulted serious neurological complications and death
• Treatment of MS with aHSCT is a promising area, but treatments are not yet FDA approved
• Legitimate trials of stem cell therapies are ongoing, but most are in phase I or II

References:

1. FDA. Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA’s new policy steps and enforcement efforts to ensure proper oversight of stem cell therapies and regenerative medicine. August 28, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm573443.htm. Accessed October 19, 2018.

2. FDA. FDA seeks permanent injunctions against two stem cell clinics: Actions part of a comprehensive approach to the oversight of regenerative medicine products. May 9, 2018. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm607257.htm. Accessed October 19, 2018.

3. Julian K, Yuhasz N, Hollingsworth E, et al. The "Growing" Reality of the Neurological Complications of Global "Stem Cell Tourism."Semin Neurol. 2018;38:176-181.

4. Bauer G, Elsallab M, Abou-El-Enein M, et al. Concise Review: A Comprehensive Analysis of Reported Adverse Events in Patients Receiving Unproven Stem Cell-Based Interventions. Stem Cells Transl Med. 2018 Jul 31. doi: 10.1002/sctm.17-0282.

5. Mancardi G, Sormani MP, Muraro PA, et al. Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis. Mult Scler. 2018;24:245-255.

6. Sormani MP, Muraro PA, Schiavetti I, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta-analysis. Neurology. 2017;88:2115-2122.