BBC – Future – The Unjustified Hypothesis on Stem Cell Treatments

Jay Shetty is 8 years old. He is smart and bright, says his mother Shilpa, though he cannot do all the things his younger brother can. “Jay doesn't sit up or use his hands as much. He is non-verbal and we do not know how good he can see, she says. "But he's playing with us and trying to copy everything his younger brother Kairav ​​is doing."

Jay has cerebral palsy. For the first few years, Shilpa was desperate to find something to help him. She scoured the internet late every night and read about a stem cell trial at Duke University in North Carolina, but Jay was not qualified. When Kairav ​​was born in 2015, Shilpa and her husband stored her son's umbilical cord blood, which was rich in blood stem cells, in the hope that another sample would emerge. It did, and this time children with sibling flora blood could participate. Was she worried about the risk to Jay? "It wasn't intrusive and it couldn't really do any harm." To raise the £ 1[ads1]5,000 treatment bill, they supplemented money they had already collected for private physiotherapy and hydrotherapy with a personal loan and additional fundraising support from the cord bank where Kairav's cord blood had been stored.

Cerebral palsy is a group of lifelong conditions that affect movement and coordination. In Jay's case, Shilpa explains, there were complications around his birth that led to the condition. There is no cure for cerebral palsy, but physical therapy, speech therapy and occupational therapy can help some symptoms. However, Shilpa hoped that Jay's stem cell therapy – a two-hour infusion in his veins – would provide benefits far beyond anything they had tried before.

We all have stem cells – these are building block cells of the type, with the ability to evolve into a wide range of specialized cell types, such as muscle, skin or brain cells. Stem cells not only replenish our old cells but also spring into action to repair and replace damaged tissue. As a result, they have been compared to our own army of microscopic doctors, but that army is relatively small.

The excitement surrounding stem cell therapy revolves around the ability to grow several of these cells in the laboratory so that they can be used to produce new tissue, replace damaged cells, and clarify disease mechanisms.

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So far, researchers have focused primarily on developing two different types of stem cells: embryonic and adult stem cells. Embryonic stem cells, derived from a growing embryo, have the natural advantage of being able to give rise to other cells in the body, an attribute known as pluripotency. However, some people have raised ethical concerns about the use of embryos in stemming these stem cells – problems that are overcome by using stem cells harvested from adult tissue. Adult stem cells are not naturally pluripotent, which means that they tend to be more specialized and thus only capable of developing into a narrower range of cell types. However, they can be reprogrammed to regain developmental flexibility.

Stem cell therapies certainly have a real promise for certain disorders. Proven and licensed stem cell-based treatments already exist for blood and immune conditions such as leukemia, lymphoma and myeloma. It is also approved in some countries for chemical burns to the eye.

The hopes of using stem cells to treat other disorders have inspired many new clinical studies and run a "stem cell tourism", centered in Ukraine, Panama and Thailand. In 2018, there were over 432 US operations at 716 clinics involved in direct-to-consumer marketing of stem cell therapy.

These clinics have a universal function: eye-watering fees – and even trials like the one at Duke. The university has a hefty price tag.

This is where crowdfunding comes into its own. A recent study in the Journal of the American Medical Association identified 408 US stem cell treatment campaigns on YouCaring and GoFundMe, with more than $ 7m applied for and 13,050 donor pledges. The clinics often encourage these campaigns: one at Northwestern Medicine has a handbook with a section on "Encouragement Methods."

Campaigns often play under potential risks or completely omit them:

"It's so simple and fast, and with only minimal side effects," claims a site that is trying to raise money for a man with Parkinson's.

"The most important thing is that it has been shown to slow the progression of the disease without any side effects," describes another and provides funds for someone with amyotrophic lateral sclerosis (ALS) – a common form of motor neuron disease.

Only 26 of the 408 campaigns mentioned & # 39; risk & # 39; and even then as risk-free or low-risk compared to alternative treatments.

It's understandable that campaigns can underplay the dangers – donors can't contribute anything else. But these cases tell a different story:

• In 2017, Doris Tyler, a 77-year-old former music teacher, raised money on GoFundMe to cover stem cell therapy in Georgia (USA) to treat age-related macular degeneration (ARMD). "We love you, Doris!" Wrote a supporter. Prior to reading, she was able to read books in large print and navigate her home. Tyler is now almost blind: “When I wake up in the morning, one of the hardest things is to open my eyes and see that everything is still dark. And it's going to be that way until I go to bed. "At least three other patients with ARMD lost sight of stem cell treatments in Florida in 2015.
• At least seventeen patients were hospitalized last year in the United States after umbilical cord blood injections. Centers for Disease Control confirmed a series of bacterial infections. Most of these patients were treated at orthopedics, chiropractors and pain clinics and received injections in the spine, knees and shoulders.
• After a stroke in the early 1960s, Jim Glass sought stem cell therapy in Argentina, China and Mexico (cost: $ 200,000). then paralyzed the right leg (the stroke had already paralyzed the left) DNA analysis indicated that the tumor originated from the injected stem cells.
• A 9 year old boy developed multiple tumors in the brain and spinal cord following stem cell transplantation. Pathological analysis confirmed that the spinal tumor contained cells from at least two donors.

Where crowdfunding campaigns do not refer to risk, there may be because some clinics themselves hardly convey it. Paul Knoepfler, a biomedical scientist at the University of California, Davis School of Medicine, attended one clinic's self-designed educational seminar (used to recruit patients and promised large discounts on enrollment). Employees, mostly dressed in medical scrubs, failed to mention potential side effects associated with stem cell transplants. However, the audience was given a credit application form to fill out. Knoepfler wrote that the experience was "more like attending a compelling entertainment show or something on a TV shopping network than an educational seminar."

In addition to under-packing the risks of these therapies, crowdfunding campaigns sometimes exaggerate the benefits.

"Treating stem cells has helped thousands of children with autism," said one. This campaign, which aims to send a young boy to Panama, has raised over $ 18,000 since September and exceeded its $ 15,000 goal.

“The ALS patients all said it reversed the damage ALS did to them! Breathing gets better, talking and swallowing make better people in wheelchairs go in two weeks, ”another said. This campaign raised $ 1,040 of the patient's $ 300,000 so far.

Nevertheless, many experts argue that these claims are premature.

There is currently no evidence that stem cell therapy is effective for autism, as Alycia Halladay, chief of science at the Autism Science Foundation, wrote in Scientific American last year. Arnold Kriegstein, a professor of neurology at the University of California, San Francisco, has similarly emphasized that recent autism tests using stem cell transplantation have not confirmed efficacy despite claims to the contrary. He describes the research as "premature."

It is particularly challenging to use stem cell treatments in ALS. Although transplanted cells are able to migrate to the injury areas, mature and integrate into the patient's nervous system before the disease begins to count (life expectancy varies, but average two to five years from the time of diagnosis), they will encounter a hostile environment with motor neurons that die around them. Currently, most studies are instead focused on using stem cells to make laboratory models of motor neurons for drug testing and disease mechanisms that can be studied. The MND Association believes that stem cell research is essential to understanding, preventing and curing MND, but states: "There is currently no reliable evidence to suggest that stem cells can be used as an effective treatment."

That Journal of the American Medical Association Study found that 43.6% of campaigns had definitive or certain statements about treatment effectiveness. It is not difficult to trace these exaggerated claims back to some clinics that use "symbols of scientific legitimacy" – published articles in journals with little or no peer review as well as implicit links to preclinical research at reputable but unrelated research centers. [19659002NoengangerharmediabidratttilåspredengrunnløsehypenI2014betaltedentidligeresoldatenJamesDeLittlediagnostisertmedParkinsons7000pundforenstamcelleprosedyreiUkrainaEtterpåsitertepressenofteklinikkenspåstandombedringhos75%avpasientene"Etterbareenavdetobehandlingenebalegenmegomåtapånesenmedlukkedeøyneogjegvarpåstedet-jegkunneikketrodet"saDeLittledengangen"MinParkinsonfølessomomdeterenfjærsomstadigtrekkermegtilvenstreMenrettetterbehandlingenføltesikkestyrkenlikesterkogbalansenminvarmyebedresometresultat"

Two years later told a deteriorating DeLittle the BBC that he felt "irritated, out of pocket and, constricted." Still, most of these readers in 2014 never knowing that the man who hoped a stem cell treatment would be "a miracle in the process" eventually concluded that it was nothing but a scam.

Patients can't even get what they paid for (let alone the previous one) effective treatments.) Lisa Fortier, researcher at regenerative medicine at Cornell University, tested nine products, but "none contained stem cells, or a single living cell of any kind." So people are potentially crowdfunding for, and donors contributing to supposed stem cell treatments that have no stem cells.

Not all stem cells are created equal. Some studies use mesenchymal stem cells – these are cells found in the bone marrow, for example, which are important for making and repairing skeletal tissue, such as cartilage, bone and fat cells. But these are now serious questions about whether they even function as stem cells. Even the person who first named them, Arnold Caplan, thinks they should be renamed to interrupt unadulterated hype about their potential: “I was wrong. I take back the name that I gave these hugely important cells. "

None of them is denying the potential for future (authentic) stem cell treatments to help some neurological conditions. Parkinson's neurodegeneration is relatively focused – dopaminergic neurons are gradually lost in a specific region called the midbrain – making it a good potential candidate for cell replacement for some of the symptoms. A Kyoto University study uses induced pluripotent stem cells, developed by programming skin and other cells to return to an embryonic-like state. These become ready to be transformed into other cell types, in this case dopamine precursor cells. "We made a hole in the frontal part of the left side of the head and transplanted around 2.4 million cells," said researchers excited about their first patient, at the beginning of their two-year trial. Parkinson's UK is still optimistic about the potential for stem cell transplants, but emphasizes that research must continue within the UK's "strict ethical and regulatory framework."

A more prominent increase in interest has centered around multiple sclerosis. Autologous hematopoietic stem cell transplantation (AHSCT) aims to replace or initiate the body's immune system: high doses of cell toxins obliterate a patient's existing immune system which is then rebuilt using their own stem cells collected before cell toxins.

AHSCT for multiple sclerosis is available in some private clinics in the United Kingdom and the NHS, albeit in a very small number of centers with limited eligibility. Treatment is aggressive, still largely experimental worldwide, and has an estimated mortality rate of 1 in 330.

Why is stem cell therapy offered in this way for multiple sclerosis (MS) in the absence of similar approaches to other neurological conditions?

"In MS, the condition has a clear immune basis, so it is much more logical to do bone marrow transplants as a way to treat the disease," explains Roger Barker, a clinical neuroscientist at the University of Cambridge. "In neurodegenerative disorders [such as Parkinson's]there is no such evidence, so there is no logic to doing this." And despite the reasonable promise of using stem cell transplants for multiple sclerosis, many patients have been left disappointed by the results – as the BBC's Caroline Wyatt recently reported in her quest to treat her own MS.

Some patients feel that they simply do not have time to wait for the culmination of good evidence from long-term clinical trials. Take this collection prayer from a patient with ALS, a condition where half of the patients die within three years of the first symptoms:

“I am down to 32% of my breath, unable to speak and lose (sic) control of my hands and legs. mine. I have a respirator for 12-14 hours a day … PLEASE HELP! "

Doesn't the patient who is" down 32% of breath "have the right to try everything that can save them, crowdfunding to do so, even if the treatment is being administered in an unregulated clinic? Barker is concerned that this vulnerability is being exploited, citing potential risks, including tumor formation.

But he also believes that legitimate stem cell research will suffer. "If things go wrong, regulators may prohibit such treatment in future periods because of the belief that these clinics essentially offer the same types of treatment as centers that have slowly worked toward clinical studies through proper rational approaches," says Barker.

Although regulators must play a role in cross-border collaboration, there is a growing consensus that crowdfunding platforms should also take responsibility. Campaigns for treatments that are unsafe or lack evidence continue to raise millions of dollars.

Protecting patients

It is true that these platforms can allow patients to explore alternatives, maintain hope and cover insurance gaps, while allowing families and friends to expand support. But shouldn't they also ban bad actors and stop the spread of misinformation (campaigns are shared hundreds of thousands of times across social media)?

Not necessarily, a GoFundMe statement to Gizmodo suggested earlier this year: “While we hope to be a useful resource for personal collection, we think it's not our place to tell them what decision to make. "Following a call for crowdfunding sites to severely vet cancer appeals to protect patients from unprovoked or dangerous treatments (such as" ozone therapy "and vitamin infusions), GoFundMe has banned users from seeking gifts for treatment in certain clinic months, and now reports that they actively evaluating fears about certain stem cell campaigns.

“As these new concerns are raised around certain stem cell clinics, we take a thoughtful approach to addressing stem cell campaigns, while continuing to provide a safe and secure place for people to gather needs and causes. We turn to experts and medical regulators in the field to understand the latest regulations and how these developments are affecting our customers, "they said in a statement.

When presented with similar concerns, JustGiving said earlier:" We don't believe we do not have the competence to judge this. "In an email to the BBC, they claimed that they ensure that all crowdfunding sites comply with legal requirements, claiming that" the safety and well-being of people using our platform, whether they raise money or make a case, is always our priority . "

Tree of Hope, a UK crowdfunding organization and children's charity, claims a different approach. Their medical committee advises on UK Stem Cell Foundation campaigns." Families turn to Tree of Hope when all other alternatives are exhausted, "says Lee Vallins, vice president and head of family support at the charity." We work with some wonderful, but often desperate parents, and ensure we work on alternatives with them, at their pace. "But even though they have supported a number of families to to raise money for stem cell transplants, there are guarantees in place.

"We easily spend time with parents calling us for advice on this type of therapy, and we quite often reject an application if parents are unwilling to consider recognized clinical studies or alternative treatment options, "says Vallins." While not one of the larger crowdfunding organizations, we certainly try to be one of the most ethical through our controls and actions throughout the process. "

Hunting for hope

Jay Shetty finally received a two-hour infusion of stem cells through a cannula into his arm at Duke University. What were Shilpa's expectations? “I knew it wasn't a cure, I knew he wasn't going to get out of it running and running. But at least I thought Jay would be able to sit up in six months, to be honest. Unfortunately, that has not happened, she says. "We have not seen any dramatic changes, but he is not so spastic, he is more conscious, to us a family we think is quite large. It is a kind of basis for all physiotherapy."

However, stem cell therapy was responsible for this improvement? Maybe Jay had acquired more skills when he grew up anyway? "It's hard to chart because we've been on therapy for a long time," says Shilpa.

To date, stem cell studies on cerebral palsy at Duke University Medical Center led by Joanne Kurtzberg did not fully live up to expectations, although work is ongoing.In 2017, 63 children with cerebral palsy were randomized to treatment (single infusion of cord blood) or placebo. They reported better outcomes at higher doses (highlighted in some media coverage), but Paul Knoefler at UC Davis School of Medicine not persuaded. "Based on the small study size, a high degree of variability in samples in the same groups, changes in the placebo group from what was expected, and the modest nature of possible differences with the higher dose relative to placebo, I am not convinced that The reported effect was meaningful, he says, and he tells me that, along with a Duke group study on autism, these results do not indicate a strong positive effect of umbilical cord cells for pediatric neurological conditions.

Cells4Life, the umbilical cord cell bank that supported Jay & # 39 ; s collection, still states on their site that "the trials on Duke have shown cord blood can reverse the symptoms of cerebral palsy." (Cells4Life states that their job is to "store each baby's cord blood." £ with an additional annual storage fee.)

The Shettys remain unprotected. "If we found a match and if Duke opens a similar try it, I pay more than happy for it, "says Shilpa. “If we have money, we will continue to do it again and again to be honest. In Jay's case, there are many empty spaces in his brain and he needs new cells. "

Meanwhile, she and other parents will continue scouring the Internet late at night, looking for something that can help their children, chasing hope, and asking for a cure. As long as they do, stem cell clinics will promise to answer the call.

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Jules Montague is a writer and neurologist in London. Her first book, Lost and Found, explores what remains of the person when the pieces of the mind are missing – from dementia and brain damage to sleep disorders and multiple personality disorders. Her second book, The Diagnosis Cure, will be published next year, exploring how medical diagnosis is deeply ingrained by the forces of trafficking, imperialism and sexual discrimination.

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