New research into a cure for MS is a mixed blessing for thousands of suffers
Shana Witcomb is excited by the prospects thrown up by stem-cell research. Who can blame her - she is 29, she has multiple sclerosis, and the words “stem cells” are being thrown around as though they're some sort of panacea. “Stem cells are capable of regenerating damaged tissue,” announces one website that offers treatment at two German clinics to people who have MS. Treatment evaluation is free; those who proceed will spend a minimum of €7,500 ( £6,800).
“I'm really hopeful,” Witcomb says. “I've spent today persuading my legs back into action because they decided to stop working. I'm just trying to stay as active and mobile as possible. I'm interested especially by stem-cell research and the potential for what that could mean in the next ten years. I'm desperately holding on.”
Witcomb is wise enough to make the distinction between stem-cell research and the stem-cell treatment available at private clinics. There is no evidence that the treatment offered by the German clinics - an injection of stem cells from the MS patient's bone marrow - has a repair function.
Early this year an uncontrolled study of 21 people, in Chicago, indicated that this kind of treatment can help adults in the early stages of MS, but researchers say that unless or until a bigger clinical trial reaches the same conclusion this one can be regarded only as encouraging, if preliminary.
Around 85,000 people in the UK have MS, and it is the most common disabling neurological condition affecting young adults. Yet there is no government funding for research into MS. The MS Society is campaigning for this, and for the introduction of controls to stop the promotion of bogus stem-cell therapies that it feels “market false hope”. Such therapies are not permitted in Britain, but companies are able to market them on the internet and to offer local phone numbers. Next month the MS Society will hold an International Stem Cell Consensus meeting for professionals with the aim of agreeing on guidance for clinicians and patients.
Without this there remains a lot of confusion and the media does not help when it reports stories of remarkable improvement that are later acknowledged as no more than placebo effect.
Witcomb, who has sold her stage-school business in Hove, regards herself as fortunate because she has intermittent relapsing MS and is being treated with the drug beta interferon. She understands why people are tempted by untested treatments: “They are desperate. People are vulnerable and it's human nature to clutch at straws. It's a hard illness because nobody can tell you what's going to happen.”
Like Witcomb, Vicci Chittenden, of Maidstone, was a teenager when she became ill, and initially she was determined not to be affected by her condition. At 57, and now with secondary progressive MS, she looks back over four decades of promises of improved treatment. “It's a bumpy road. Every time you read of some new treatment you think, ‘wow!' Then you realise you don't meet the criteria for the trial. So you sit at home, your MS is progressing, and you think, where is this going? It feels like your body is turning into concrete.”
Three years ago she spent thousands of pounds on stem-cell treatment at a Rotterdam clinic. It made no difference to her health and the clinic is under investigation, but while Chittenden is embarrassed to have used money donated by family and friends, she doesn't regret the treatment. Her reaction explains why stem-cell treatment for MS is given so much credibility. “I was over 50, disillusion started to set in and I felt I had nothing to lose. I almost felt I was letting myself down if I didn't do it. I went into it with my eyes open and I enjoyed the trip. You have to have hope.”
Paul Goldberg is more sceptical. At 68, he has had MS for almost 40 years and his condition has reached the secondary progressive stage but he remains mobile, largely because of his irascible attitude to his condition and a rigid diet and exercise regime, he believes. “I don't get carried away, I'm rational,” he says. “I'd like to dip charlatans slowly into a pot of boiling oil. It's a pity that the controls by the authorities have so many holes. The desperation I can understand because as I've got older and as MS has kicked in, I can't play with my grandchildren properly and I used to be a crack basketball player.
“Anything that offers a restitution of even part of that, you say, 'Oh yes please, I want that'. But I don't believe anything unless it's proved to me. I had an internet offer from a Dutch organisation, which I almost believed (using stem cells from your bone marrow) but when I checked with doctors they said stem cells don't work like that.”
Goldberg, who lives in Totteridge, North London, also tells me that he has just started to take low-dose Naltrexone, a drug used to treat addictions, which is gaining credibility as a treatment for MS. Its use in this context is not licenced in the UK and is supported only by small pilot clinical trials. “I know it works because I'm using it,” he says. “You could say it's a calculated experiment.”
Clinicians are aware of the emotive nature of discussing a cure for MS, and weigh their words carefully. At the University of Cambridge, Robin Franklin, professor of neuroscience at the MRC Centre for Stem Cell Biology and Regenerative Medicine, acknowledges that the proliferation of vague and misleading information about stem cells on the internet makes it hard for a lay person to pin down definitive information about stem-cell treatment, or about future treatment.
“Even among scientists there is no consensus about what is meant by a stem cell in the brain,” he says. “The frustration comes from the ambiguity around stem cells and misunderstanding about what stem cells are trying to achieve. In the context of MS, stem cells can be helpful for two distinct components of treatment: to try to stop damage and to try to repair it.”
The problem for those of us outside the medical community is that we tend to confuse these two forms of treatment. The first involves mesenchymal stem cells from the bone marrow designed to deal with the immune system; the second involves brain stem cells designed to repair the brain when it can no longer do so itself.
These are the challenges that face MS researchers. At the University of Edinburgh, Charles ffrench-Constant, professor of medical neurology at the MRC Centre for Regenerative Medicine and Centre for Multiple Sclerosis Research, explains the significance of the recent Chicago study. “What it's telling us is something we suspected: that early in MS the patients' brains repair quite efficiently. But as the disease progresses so the repair in most patients will fail and that causes progressive disease. Blood stem-cell transplants are probably working either by suppressing or resetting the immune system. There are a number of drugs available, and if studies found them to be effective that would be preferable to the procedure and cost associated with a transplant.”
Both specialists point out that stem-cell treatments being offered abroad don't target the repair capacity of the brain. For some therapies on offer there is little or no scientific rationale behind them. “Many of the treatments are predicated on the assumption that if you inject stem cells into the body they would automatically do what's required,” ffrench-Constant says. “We know that's not true.” Of course research literature is full of apparently hopeful results that failed to withstand a controlled trial. But Franklin and ffrench-Constant are confident that drug treatment will eventually do the work being promised by stem-cell treatment.
This is likely to take two forms. The first will suppress the immune system and this treatment is in the early stages of trials, ffrench-Constant says. “It would be irresponsible to advise MS patients to rush to their neurologist and say ‘I've heard about this treatment and I want it'. Neurologists either will or won't be involved in trials and, if they are, they will know which patients they're going to select. Having sat in clinics I know the frustration that patients will feel and I wish I could solve it, but it takes a decade to get a drug from the discovery stage and out into general clinical use and many of these drugs are halfway down the track. There's still quite a long way to go.”
The second form of drug treatment will promote repair by mobilising the brain's own stem cells. At the moment no drug going through clinical trials has this objective, but there are credible candidates, Franklin says. “It is possible that in the next five years we'll see trials starting where drugs will be used to try to promote repair by the brain's stem cells, but the timelines are difficult to predict.”
What is MS?
MS is an auto-immune condition. The immune system, which normally helps to fight off infections, mistakes your body's tissue for a foreign body and attacks it. In MS, it attacks myelin, a protective sheath surrounding nerve fibres of the central nervous system. When myelin is damaged, this interferes with messages between the brain and the rest of the body. There can also sometimes be damage to the nerve fibres and this causes disability. For some people, MS is characterised by periods of relapse and remission, for others it is progressive. Due to the variety of symptoms it is hard to diagnose.
Stem cells are unspecialised cells which can develop into almost any cell in the body. They are found in early embryos, foetuses, umbilical cords and in small amounts in adults.
What makes them important in MS research (and other diseases affecting the nervous system) is that they have the potential to grow into new nerve cells and cells which make myelin.
The facts about stem-cell tourism
There has, justifiably, been worldwide excitement over the therapeutic promise of stem cells derived from embryos and adults. They are touted as little short of a miracle: inject them into brains to restore the cells lost to Parkinson's disease; inject them into the spines of the paralysed to make them walk again.
But, mostly, hope is miles ahead of reality. Only a few clinical trials are being conducted with human patients (two in the US, one in the UK). Despite this, a number of medical clinics are jumping the regulatory gun and offering stem-cell therapies straight to the patient.
The treatments are offered in regulatory black holes abroad where scientific expertise is cheap and abundant, but oversight is lacking.
The rise of stem-cell tourism is causing great concern in the scientific community. Last month, a medical journal reported a case in which an Israeli teenager, born with an inherited neurodegenerative disease and confined to a wheelchair, was taken to a Russian clinic for stem-cell therapy. It was discovered later that the stem cells had caused non-cancerous tumours to sprout on his spinal cord and brain stem.
The tumours came not from the boy's own body, but from the stem cells derived from two foetuses, including a female. Once in the boy's brain, the stem cells began growing out of place and out of control. The brain stem tumour, while non-malignant, is inoperable; if it grows, he will die. The Russian clinic involved has declined to reveal much to the boy's physician.
It is just another case in a growing list of stories about stem-cell tourism. This month, the journal Science also highlighted the problem, citing the fact that companies can market directly to internet-savvy patients, without a referral from medic professionals. For example, the website for Medra, which claims to have the only US physician offering foetal stem-cell therapy - Dr William Rader - is awash with positive testimonials. But it has proved difficult for other scientists to obtain information on Medra's cell lines; the website says only that they come from Eastern Europe.
Some companies use blogs and YouTube to feature patient experiences and yet, in the clinical world, the hallmark of success, or failure, is a controlled clinical trial with the results reported in a peer-reviewed medical journal. There are some positive developments: regulatory agencies have shut down clinics in the Netherlands and Ireland.
The article in Science calls for the guidelines from the International Society for Stem Cell Research (isscr.org) to be disseminated more widely, and for the World Health Organisation to adopt a firm position on the use of stem cells.
Times Online, 6th April 2009
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