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1 Stem cell therapy

2 We hope you find the information in this factsheet helpful. If you would like to speak with someone about any aspect of MS, contact the MS Trust information team and they will help find answers to your questions. This factsheet has been provided free by the Multiple Sclerosis Trust, a small UK charity which works to improve the lives of people affected by MS. We rely on donations, fundraising and gifts in wills to be able to fund our services and are extremely grateful for every donation received, no matter what size. MS Trust information service Helping you find the information you need The MS Trust offers a wide range of publications, including a newsletter Open Door, which provides an ongoing update on research and developments in MS management. In addition it contains articles from people with MS and health professionals. For a full list of MS Trust publications, to sign up for Open Door and much more visit our website at phone (from a mobile) (Lines are open Monday - Friday 9am-5pm) write infoteam@mstrust.org.uk MS Trust Spirella Building Letchworth Garden City SG6 4ET Reg charity no

3 Stem cell therapy Date of issue: January 2016 This factsheet will be reviewed within three years Contents 1. What are stem cells? 3 2. How could stem cells treat MS? 5 3. How is stem cell treatment given? 8 4. Results of stem cell clinical trials in MS Is stem cell treatment available for MS? Key considerations References and further information 24 Summary Stem cells are different from most cells in the body as they have not yet developed to carry out a particular function. Researchers are exploring whether it is possible for stem cells to become cell types which could slow MS disease activity, repair existing damage or replace faulty parts of the immune system or nervous system. Stem cell therapy is already being used for other conditions, such as cancer of the blood (leukaemia). Stem cell therapy is a largely experimental treatment for multiple sclerosis (MS) and is being tested in clinical trials. A type of stem cell therapy, called autologous haemopoietic stem cell transplantation (abbreviated to AHSCT, ASCT or HSCT) has been most extensively studied. AHSCT uses high doses of chemotherapy to wipe out harmful cells in the immune system so is more intensive and higher risk than most other treatments for MS. The immune system is then rebuilt using stem cells collected from your blood before chemotherapy. The idea is to reboot the immune system so that it no longer attacks the brain and spinal cord to cause further damage. 1

4 So far, only a limited number of small scale clinical trials have taken place but early results are encouraging and understanding of how best to treat people with stem cells is improving. More clinical trials are needed to work out which types of cells and which route of delivery would be most effective and how different types and stages of MS disease can be targeted. The field of stem cell therapy for MS is developing rapidly, including our understanding of its safety. Currently, AHSCT has not been formally assessed for use in the NHS outside clinical trials, although some centres are able to provide it under specific circumstances to a very small number of people. People accepted for treatment generally either have a very aggressive type of MS or continue to have relapses even after trying one or more disease modifying drugs. Stem cell therapy is a complex procedure which involves a lot of technical language. More information is available below. You might like to ask your MS nurse or other members of your MS team to explain further or you can contact the MS Trust Information Team. 2

5 1. What are stem cells? Most cells in the body have developed to carry out very specific functions, such as being a nerve cell, a red blood cell or a heart muscle cell, and can t go on to change their function. They are called specialised cells. Stem cells are part of the body s normal repair system which replaces damaged or dying cells where possible. Stem cells have not yet developed to carry out a particular function so are described as unspecialised. Each stem cell has the potential to develop into one of a number of different specialised cell types depending on the body s needs at a particular time. Types of stem cells There are several types of stem cells. Those most commonly considered for treating people with MS at the moment are: Mesenchymal (pronounced mez-en-kee-mal or mez-en-kai-mal) stem cells which are found in the bone marrow and also in placenta, cord blood and some other adult tissues. They usually develop into bone, cartilage and fat cells. Haematopoietic (pronounced hee-mato-poy-etic) stem cells which are found mainly in the bone marrow although small numbers circulate in the blood. They develop into the different types of cells found in the blood including some cells which are part of the immune system. They are produced in large numbers throughout our lives and continually replenish our blood and immune system. Neural stem cells which are found in the brain and can develop into various types of brain cell including oligodendrocytes and neurons. Although of great potential, their use is at a very early stage of development. Induced pluripotent stem cells do not occur naturally in the body. They are cells that have already specialised but then been reprogrammed in the laboratory to behave like stem cells. They may be useful in therapies in the future but research is still at a very early stage. 3

6 Sources of stem cells Stem cells can be obtained from human embryos, umbilical cord and placenta or from adults. Early on, researchers considered using stem cells from embryos because they can potentially mature into most types of cells in the body and so they could offer many possible avenues for therapy. However, the ethical and practical aspects of obtaining and using cells from human embryos are complex, and the recently developed ability to make stem cells of very similar character using induced pluripotent stem cell technology to reprogramme adult cells in the laboratory, has led to embryonic cells being much less often used now. Blood left in the umbilical cord and placenta after a baby is born contains stem cells and is relatively easy to collect. This blood contains haematopoietic stem cells and may also contain other types of stem cell although this is not certain yet. Stem cells collected from adults are more limited in the range of cells that they can mature into. However, they are relatively easy to obtain from the bone marrow or blood, and other tissues such as adipose tissue (fat). They carry the additional advantage that they can be taken from the individual to be treated and so, when re-injected, they do not trigger the rejection reaction that the body would mount against cells or tissue if they were foreign (from a donor). 4

7 2. How could stem cells treat MS? What happens in MS? MS is often thought of as a combination of two broad disease processes, one characterised by inflammation and the other by neurodegeneration. The relationship of the neurodegenerative processes to inflammation is not yet well understood. During inflammation, the body's immune system starts to mistakenly attack cells within the central nervous system. Part of this attack is directed at myelin, a fatty protein that forms a sheath around the axon of a nerve cell, the long thin part of the cell that transmits electrical messages. Myelin acts like insulation and helps maintain the speed of transmission of messages. In the central nervous system, myelin is produced by cells called oligodendrocytes. If your MS is predominantly in the inflammatory phase, you will experience relapses and your MRI scans may show new active lesions. As the body repairs the damage caused by the immune system, or reroutes messages around the areas of damage, your symptoms will improve although they may not go away completely. In the degenerative phase, the body cannot manage to repair all the damage to nerve cells and they gradually die back. This is called neurodegeneration. If your MS is at this stage, you will experience a steady increase in symptoms and disability which is known as progression. Some people will experience inflammation and progression at the same time, particularly if their MS is in a transitional phase, moving from relapsing MS to secondary progressive MS. Research strategies for stem cell therapy in MS Stem cells could be used in a range of different ways to replace faulty, damaged or missing cells in the immune system or in the brain and spinal cord. Any cells that are involved in MS disease activity are potentially a target. The strategies 5

8 being used in MS research can be divided into three categories, each looking to use different types of cell. They are: Firstly, to replace or reset the body s immune system so that it no longer attacks myelin or causes inflammation in the brain and spinal cord. This type of treatment uses haematopoietic stem cells, those stem cells present in the bone marrow that are responsible for making the components of blood. The second strategy is to protect nervous tissue from damage and to encourage the repair of existing damage. This treatment uses other types of cell present in the bone marrow, or sometimes in other tissue such as fat underneath the skin, that have repair properties, including mesenchymal stem cells. The third is to replace damaged oligodendrocytes or restore their ability to make myelin. This treatment would probably use induced pluripotent stem cells which can turn into oligodendrocytes but this form of stem cell therapy for MS is at a very early and experimental stage. As MS seems to have two disease processes, inflammation and neurodegeneration, different types of stem cell therapy may be needed to reduce inflammation and to encourage repair. Types of transplantation The following is a guide to some of the therapies that are showing the most promise in treating MS. Firstly, hematopoietic stem cell transplantation (HSCT), which is a type of immune ablative bone marrow transplantation. HSCT is the transplantation of stem cells that can develop into the cells of the immune system and blood. The aim is to reboot your immune system by killing the immune cells that were attacking your brain and spinal cord, using cancer chemotherapy drugs, and replacing them with a regenerated immune system which may be less aggressive. 6

9 HSCT is a well-established treatment for some cancers of the blood and bone marrow, such as leukaemia and non-hodgkin lymphoma, but is generally only used if other treatments have failed. Most research studies exploring HSCT use the person s own bone marrow stem cells, collected and injected back into their body. This is called autologous HSCT (AHSCT or ASCT). This minimises the possibility of them being rejected. AHSCT is the type of stem cell transplantation which is most advanced as a possible treatment for MS. If the stem cells come from someone else (a donor) it is called allogeneic transplantation. This is now very little explored in MS, as it is associated with a higher risk of complications and death. The second form of cell therapy in MS also uses cells from the bone marrow, but the focus is quite different. Bone marrow, in addition to haematopoietic stem cells, includes many other cell types, and some of these have potentially important properties that both protect cells from disease processes and promote repair. Mesenchymal stem cell transplantation (MSCT) uses one such cell type; mixed mononuclear cell therapy (MMCT) pools all these different bone marrow cells and uses them together. These forms of cell therapy do not aim to replace the person s own immune system, and so do not require pre-treatment with cancer chemotherapy drugs. The third form of cell therapy, using stem cells to replace oligodendrocytes and so, hopefully, to regenerate myelin, is still at a very experimental stage, though early clinical trials to test its safety are currently being planned, particularly in the USA. 7

10 3. How is stem cell treatment given? Autologous haematopoietic stem cell transplantation (AHSCT) is just beginning to be offered to a very small number of people with MS outside of clinical trials, generally after other treatments have failed, and so is described in detail below. AHSCT treatment procedure Mobilisation, also called in vivo purging, is the first stage of the AHSCT procedure. Only a small number of stem cells are naturally found in the blood. More can be obtained by encouraging them to move from your bone marrow, where they are formed, and to enter your blood stream so they can be collected. This movement is called mobilisation. Mobilisation is carried out by giving an infusion (through a drip) of chemotherapy (cyclophosphamide) and injections of a synthetic form of a natural growth factor called G-CSF (granulocyte-colony stimulating factor). Your MS symptoms may get temporarily worse during this phase. Harvesting (collecting) your stem cells happens about 10 days after mobilisation once blood tests show that there are enough stem cells present in your bloodstream. It takes between half a day and one day. You will be connected to a cell-separator (apheresis) machine which collects your blood through a needle in your arm, separates out the stem cells and then returns all the other components of the blood to your body. Cryopreserving is when your harvested stem cells are frozen until you return to the hospital for the transplant stage of the procedure. Conditioning chemotherapy gets your body ready for the return of your stem cells. It may involve either completely eliminating (myeloablative or high intensity chemotherapy) or partially eliminating (non-myeloablative or low intensity chemotherapy) your bone marrow and immune system and so hopefully destroying the cells that are involved in MS disease activity. More recent procedures for people with MS have favoured lower intensity chemotherapy. Conditioning chemotherapy is likely to take several days. You 8

11 may need to take drugs to control nausea and vomiting which are common side effects of chemotherapy. You may also be given steroids to dampen down any immune reactions. Transplantation, also known as stem cell return, is when your stored stem cells are thawed and returned to your blood by infusion (through a drip). This is often a couple of days after the conditioning chemotherapy and will only be done once all the chemotherapy drugs have cleared from your system. It takes a couple of hours and is similar to having a blood transfusion. The stem cells make their way to your bone marrow (engraftment) and should start making new blood and immune cells within 10 to 30 days. During that 10 to 30 day period, you have, in effect, no immune system which explains some of the risks and side effects set out below. Risks and side effects Susceptibility to infection, also known as being immuno-compromised, is common immediately after conditioning chemotherapy and until your immune system has been rebuilt by your stem cells. You should be closely monitored by your health professionals to make sure that you remain as well as possible and you are likely to be in an isolation room in hospital for several weeks. Both you and your visitors will need to take precautions to avoid introducing any infections. What might normally be a low threat to your health can be very serious, even life threatening, when immuno-compromised. Previous infections, particularly with the viruses that cause shingles, cold sores and herpes, may become active again. You may be given antibiotics and transfusions to support you through this vulnerable time. Development of autoimmune conditions is possible, particularly autoimmune thyroiditis where the body sees the thyroid, and the hormones it produces, as threats and so attacks them. Side effects of chemotherapy can include fatigue, weakness and a temporary loss of appetite. You will be at increased risk of bleeding and bruising and your 9

12 MS symptoms may also be worse for some time. Hair loss is common but should only last between one and six months although your hair can grow back a slightly different colour or texture. Other longer term side effects can include lowered fertility or early menopause if high dose chemotherapy has been used. Recovery from such a complex, aggressive procedure can take a considerable time and you can expect to be off work. You may need three to six months to get back your normal amount of energy and to resume your previous level of activities. Some people take over a year to recover. There is a risk of dying due to the procedure. Although treatment procedures are improving, clinical trials since 2001 have still had treatment-related death rates of one or two people in every 100 (1.3%), according to analysis by the European Group for Blood and Bone Marrow Transplantation (EBMT). The majority of deaths were due to infections. Health professionals who should be involved A neurologist with specialist expertise in MS should always assess your suitability for treatment. As clinical trials have shown that not everyone with MS responds to treatment, hospitals will usually only treat people whose MS meets strict criteria. The criteria will vary between medical centres but the neurologist will probably be looking for evidence that your MS is still in the inflammatory stage and that any disability is not too well established. The neurologist may also look for evidence of: relapses continuing despite trying one or more of the disease modifying drugs active inflammatory disease seen on recent MRI scans including gadolinium enhancing lesions low levels of well-established disability as this is a measure of neurodegeneration. Often disability is measured using the EDSS scale and an EDSS score below 6.0 would be a typical requirement. An EDSS of 6.0 means being able to walk at least 100m with or without using a single walking aid and with or without resting. However, the time since your diagnosis may 10

13 also be taken into account as people with a very long disease course are less likely to respond to treatment. After treatment, an MS specialist neurologist should assess your response. A haematologist is a doctor who specialises in the diagnosis, treatment and prevention of blood diseases. Haematologists are experienced in using AHSCT to treat blood cancers and some other conditions and will supervise the procedure. The haematologist and their team will want to be sure that you are well enough to withstand the relatively aggressive treatment procedure. Some of the medication used in the conditioning and recovery process can occasionally cause problems with your internal organs, so it's important to know how well they are functioning before treatment begins. They may carry out: blood tests including measuring the levels of different cell types in your blood a physical exam tests to check that your heart, lungs, kidneys and liver are working well tests for existing infections a check on your medical history to see if you have previously had treatments that involve suppressing the immune system. During treatment, you will mostly be under the care of the haematology team and they will be involved with your after care to ensure that you make a good recovery. An AHSCT multidisciplinary healthcare team should coordinate your assessment, treatment and care. It should include an MS specialist neurologist and a haematologist as well as other relevant health professionals such as AHSCT specialist nurses, physiotherapists, occupational therapists, counsellors and dieticians. 11

14 Regulation of stem cell therapy In the UK, any hospital performing transplants, including stem cell therapy, must be accredited by the Joint Accreditation Committee-ISCT & EBMT (JACIE). The transplant centre has to show that procedures are being carried out to agreed standards by suitably trained staff. Accredited centres are inspected regularly to make sure that these standards have been maintained. JACIE standards have been adopted in some other countries. You can see JACIE accredited centres in the UK and abroad on a map on the JACIE website at Other countries may have their own standards, for example FACT in the USA. 4. Results of stem cell clinical trials in MS Clinical trials of stem cell therapies are the best way to find out which types of cells and which route of delivery are most effective. They can also determine which types and stages of MS can be targeted. This is a growing area of research but, so far, only a limited number of small scale clinical trials have taken place. Early results are encouraging and understanding of how best to treat people with stem cell therapies is improving. The results of longer term clinical trials will be essential in assessing effectiveness and safety before stem cell therapies can be made widely available to people with MS. Autologous haematopoietic stem cell transplantation (AHSCT) In 2014, researchers summarised the results of 23 clinical trials of AHSCT as a treatment for MS. They found that 538 people with MS had undergone treatment as part of a trial of whom 336 (62%) had primary or secondary progressive MS. Early trials included more people with progressive MS but more recent trials have included more people with relapsing MS. All the studies reviewed were small trials ranging from 5-74 participants. 12

15 The review found that only four of the 23 studies provided data and information on the safety and long term effects, generally up to two years after the transplant. Due to the differences in the participants' characteristics, treatment methods and ways of assessing the outcomes, the authors found it very difficult to compare the results of the studies directly and to draw definitive conclusions. However, they highlighted that: treatment was more successful in people who had active inflammatory disease (usually relapsing remitting MS but sometimes early secondary progressive MS), a short disease duration and less disability as judged by a lower EDSS score, a common measure of disability between 36% and 100% of participants experienced no progression of their MS two years after treatment as judged by their EDSS score. Only a small number experienced an improvement in their MS using this measure. This suggests that AHSCT could prevent disability progression in the short term but not reverse existing damage. Only a few studies looked at disability progression in the longer term, generally more than two years after treatment. All observed an increase in the number of people whose MS progressed showing that MS disease activity had not been halted completely. The review found some risks and side effects of AHSCT treatment. These included: reactivation of MS disease activity, where symptoms worsened, during the mobilisation phase of treatment. Mobilisation is when stem cells are prompted to move into the blood stream before they are harvested sepsis, a severe response to infection, and urinary tract infections which were reported in almost all studies reactivation of previous viral infections, for example, varicella-zoster virus, which causes shingles, and herpes simplex virus, which causes cold sores or herpes 13

16 development of autoimmune diseases, particularly autoimmune thyroiditis, where the body sees the thyroid, and the hormones it produces, as threats and so attacks them malignancies (cancers) although these were unusual in the relatively short period of follow up. Further follow up will be needed to be sure that cancer risk is not increased in the longer term deaths that occurred as a consequence of transplantation. They ranged from 1 in every 40 people (2.5%) treated to 1 in 5 people (20%) in the studies that were reviewed. An analysis of more recent studies suggests that that the risk of death is now 1.3% (equivalent to 1 or 2 people in every 100 treated). This reduction is probably due to changes in the selection criteria for clinical trials which are now less likely to include people who have lived with MS for a long time or who have well established disability. In addition, changes in the AHSCT procedure to using less aggressive conditioning chemotherapy have reduced the risks. The reviewers conclude that AHSCT might be most appropriate for people with aggressive, relapsing remitting MS for whom treatment with Tysabri (natalizumab) or Lemtrada (alemtuzumab) has not worked or cannot be considered. In addition, a small group of people with exceptionally active MS could be considered for treatment. More detail on the design and results of AHSCT trials is available in reviews from Holloman et al. in 2013 and Radaelli et al. in 2014 (see section called References below). The focus of AHSCT research is now on clinical trials which compare participants randomly allocated to either AHSCT or a dummy treatment (or potentially to other treatments), use lower intensity conditioning chemotherapy, include a larger and more diverse group of people with MS and assess the results with a range of measures. In addition, it will be important to follow up people who have had treatment to see what improvement, and what side effects, they experience in the longer term. 14

17 Current treatment protocols are most effective in the inflammatory phase of MS. It seems clear that progression is not affected in the long term so different treatment approaches will be needed to slow or halt progression. Mesenchymal stem cell (MSCT) and mononuclear cell transplantation Research using animals with a form of laboratory-induced MS has demonstrated the potential of these cells to alter the response of the immune system and protect nerves from damage. Several clinical trials have shown that these forms of cell therapy appear safe and may be useful as a treatment for people with MS. However, trials are generally only at the Phase I stage so this approach still lags behind AHSCT research. However, this approach to cell therapy does not involve chemotherapy, and therefore has far fewer risks than AHSCT so researchers remain optimistic. The results to date are summarised in a review by Holloman et al. in 2013 (see section called References below). Future directions for stem cell research in MS The UK research community is very active in this area and includes groups in Bristol, Cambridge, Edinburgh, Nottingham, Sheffield and several teams in London. Most centres undertake research in the laboratory and with people with MS in the clinic. Stem cell treatments have huge potential for the future treatment of people with MS but the disease process in MS is still poorly understood so more information is needed. Key questions for research include: How can stem cells be encouraged to develop into cell types that can treat MS? Which cells or systems in the body should be targeted? Why do some people benefit more than others from treatment? The results of these avenues of research should allow the design of more effective clinical trials and produce better outcomes for people with MS. 15

18 5. Is stem cell treatment available for MS? Treatment with stem cells is well established for other conditions. For example, it is already used to treat some cancers of the blood and bone marrow, such as leukaemia and non-hodgkin lymphoma, but is generally only used when other treatments have failed. The use of stem cell treatments for people with MS is at a much earlier stage of development. It is not yet carried out routinely and treatment protocols have not been standardised. Treatment may be available through a clinical trial or, rarely, outside a trial if the clinical need is clear. Only AHSCT is available as other forms of stem cell therapy are at a very early stage of development. Getting treatment through a clinical trial There are currently some clinical trials taking place in the UK to test experimental stem cell therapies in people with MS. Each of these has a different approach and some are comparing stem cell treatment against placebo (dummy treatment) which means that there is only a 50/50 chance of participants receiving the stem cell treatment. If you are interested in taking part in a clinical trial, it will be important to check the inclusion criteria (characteristics that you must have to be included in the study, for example, your type of MS, age, EDSS score) and exclusion criteria (characteristics that disqualify you from participating). You will need to consider what is involved, for example travelling to attend many appointments for tests and follow ups for several years, as well as the possible risks and benefits. UK clinical trials which are recruiting We are only aware of one clinical trial which is recruiting participants in the UK at the moment. MIST (Multiple sclerosis International Stem cell Trial or Stem Cell Therapy for Patients with Multiple Sclerosis Failing Alternative Approved Therapy; NCT ) is recruiting in Sheffield. It is part of a multi-centre trial 16

19 administered by Northwestern University in Chicago. Only a small number of people, around one or two per month, are being recruited in the UK. If you are interested in joining this trial, you should check the inclusion and exclusion criteria on the Clinical Trials website If you are eligible, you would need a referral from your usual neurologist or GP to Professor Basil Sharrack, the neurologist, and Professor John Snowden, the haematologist, at Sheffield who are running the trial. Ongoing UK clinical trials which are no longer recruiting Currently (December 2015) four clinical trials of stem cell therapy in MS are listed for the UK on the Clinical Trials website ( but none of them need more participants. They are included here for information only. The trials are: MSCIMS (Mesenchymal Stem Cells in Multiple Sclerosis; NCT ), based in Cambridge and London which has already completed. STREAMS (Stem Cells in Rapidly Evolving Active Multiple Sclerosis; NCT ) administered by Imperial College, London which has already recruited all the participants needed. ACTiMuS (Assessment of Bone Marrow-derived Cellular Therapy in Progressive Multiple Sclerosis; NCT ) in Bristol. The MS Trust is one of the funders of this research. No new participants are currently needed. SIAMMS-II (Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis; NCT ) in Bristol which is following up people who took part in the first SIAMMS trial and is not recruiting new participants. Looking for new stem cell clinical trials in the UK More clinical trials may take place in the UK in the future. You can check for any new trials on the Clinical Trials website ( using the search term multiple sclerosis AND stem cells and then using the map function to focus in to the UK. 17

20 Treatment in the UK outside a clinical trial Until recently, treatment with stem cells was seen as purely experimental for people with MS and was only available in the UK through clinical trials. However, treatment is becoming available through the NHS at a very small number of JACIE accredited centres. The number of centres with experience of AHSCT for people with MS is very limited in the UK and the number of people who are accepted for treatment is likely to remain extremely small. On the NHS in England, AHSCT is not routinely considered but may be an option after discussion between the haematology and MS teams. People are usually only accepted if they have a very aggressive form of MS or if they continue to have relapses even after trying one or more of the disease modifying drugs. Each hospital will have its own specific eligibility criteria but they may follow the guidelines developed by the European Group for Blood and Marrow Transplantation (see Snowden et al. (2012) in the section called References below). Based on the data from clinical trials, people are more likely to respond to treatment, and therefore be suitable for AHSCT, if they meet the following general criteria: relapsing MS or progressive MS with evidence of continuing inflammatory disease, for example, active lesions are seen on recent MRI scans continuing relapses even when on disease modifying drug treatment (at least one drug tried - though others have suggested (see above section on the results of clinical trials of AHSCT) that AHSCT should only be considered in people who have relapses even after treatment with Lemtrada (alemtuzumab) and/or Tysabri (natalizumab), or in whom these drugs cannot be considered) early in the MS disease course before the onset of significant irreversible disability. Disability is often measured using the EDSS scale. Exact requirements will vary but would typically require the ability to walk at least 100m with or without using a single walking aid and with or without resting (EDSS of 6 or below) 18

21 fit enough to undergo the treatment regimen. In addition, people with very aggressive MS, who have developed severe disability in the previous year, may be accepted for AHSCT. If you are considering AHSCT, you would need to be referred by your usual neurologist or GP to the relevant haematologist and neurologist. Both specialists would need to assess your suitability for treatment. Treatment outside the UK There are clinics around the world that offer stem cell treatment for MS on a commercial basis. This is sometimes known as stem cell tourism. Overseas clinics may accept people whose MS does not fit the usual criteria for treatment in the UK including people with progressive MS without ongoing inflammatory activity. This is a group that we already know do not respond to AHSCT, so this is something that you will want to take into account if you are considering treatment abroad. The cost of treatment varies widely but can be between 30,000 and 85,000. Not all these overseas clinics will be working to the same standards of safety or offering the same level of support during treatment as must be provided in the UK. This is part of the reason why these clinics often base themselves in countries with less rigorous healthcare regulatory systems. If you are considering going abroad, it will be important to find out: exactly what kind of treatment is provided whether the clinic is regulated to international standards that others have benefited from treatment at this clinic what follow up is provided how safety, side effects and the effectiveness of treatment are monitored over time 19

22 what is, and is not, included in the price quoted and what you will need to pay for in addition to flights and possibly hotel accommodation. The risk of having additional costs may be high if you develop complications after the initial treatment. If you are considering treatment abroad, it will be essential to make sure that there will be proper follow up and support once you have returned to the UK. It is important to be cautious as there have been examples in the past of unscrupulous people making a profit by offering worthless treatments to people with MS at very high cost. Some clinics do not even check whether a person has MS or not. 20

23 6. Key considerations When considering any treatment, it is vital to weigh up all the different factors, discuss your options with health professionals, family and friends before deciding what seems best for you as an individual. It is important to look critically at the risks and not only the hope that is offered. Below is our list of suggested actions if you, or someone you care about, think that AHSCT may be an appropriate treatment option: Get independent information If you would like to know more about stem cell therapies, it is important to seek accurate, unbiased information from trusted sources. The MS charities and independent stem cell organisations, such as EuroStemCell, the International Society for Stem Cell Research and the European Society for Blood and Marrow Transplantation are a good place to start for a balanced overview. You can access some of their factsheets and other information using the links in the section below called Further information. The MS Trust will keep the information in the A-Z of MS about stem cell therapy for people with MS on its website under regular review. Information about treatment and developments in stem cell research will be updated. Seek the opinion of your MS specialist team It will be important to consult your MS team as they know you and your MS well. If your relapses are not well controlled by a disease modifying drug, they may suggest that you try an alternative. In some circumstances, your MS team may agree that AHSCT is appropriate. You will need a referral from your neurologist to take part in some clinical trials or to attend most hospitals providing AHSCT. You may need to provide some evidence of your MS disease activity, such as a recent MRI scan, or your history of previous treatments. Your MS team will remain involved with your longer term care once you have recovered from the AHSCT procedure and no longer need the involvement of the AHSCT multidisciplinary team. 21

24 Check the credentials of the AHSCT team In the UK, any centre performing transplants, including haematopoietic stem cell therapy, must be accredited by the Joint Accreditation Committee-ISCT & EBMT (JACIE). JACIE standards are also used in some countries outside the UK. You can check for licensed centres on the map provided by JACIE at Some other countries have their own system of regulation. If you are considering treatment abroad, it will be important to check that similar regulation is in place to JACIE. You should check that the hospital where you will be treated has experience of stem cell transplantation in people with MS as it is such a new treatment so worldwide experience is limited to a few centres. You can visit the websites of clinics offering treatment to understand exactly what they offer and to whom, the process you would need to go through, the cost and any follow up support that is available. You could ask the clinics for any information sheets and eligibility criteria. Treatment should include assessment by an MS specialist neurologist and a haematologist who work together as part of an AHSCT multidisciplinary team. Treatment should be explained in a written informed consent document in a way that you can easily understand. You should have the opportunity to ask questions at all stages of the process. Clinic websites will probably include personal stories but may only show you their most successful cases. You may be able to get a more accurate idea of success rates by asking on forums or groups, such as Facebook, although, inevitably, people are more likely to talk about successes than side effects, complications or failure. Some people with MS have blogged about their experiences of having stem cell therapy. Balance the risks and benefits to your health Stem cell therapy has the potential to bring significant benefits to some people with MS. Good progress is being made through clinical trials and the outcomes of treatment are improving as more is learned. However, as research is still at an early stage, stem cell therapy is not widely practiced and the results of treatment 22

25 for a particular person cannot be predicted. The risks (see above) should be very carefully considered, including the possibility of treatment-related death, and weighed up against the potential benefits. Find out about after care Find out what care will be available after your AHSCT treatment especially if you are considering going abroad. What support will be available if you experience complications or side effects? This should be outlined exactly so that you know what to expect and who to contact if you have any concerns. Consider the costs Treatment in a clinical trial should be free. In addition, a very small number of people are being accepted in the UK for treatment on the NHS. The quotes for treatment abroad vary widely but typically range from 30,000 to 85,000. Before making any commitment, it will be important to establish the full costs of treatment including assessment, tests, treatment and follow up appointments. You will need to budget for your travel and for hotel costs for anyone going with you. You may also need accommodation for yourself if you are discharged from hospital but don t feel strong enough to travel home straight away or if you develop complications and need to extend your stay. 23

26 7. References Burt RK, et al. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2015; 313(3): Holloman JP, et al. The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis. American Journal of Stem Cells. 2013; 2(2): Radaelli M, et al. Autologous bone marrow transplantation for the treatment of multiple sclerosis. Current Neurology and Neuroscience Reports. 2014; 14(9):478. Snowden JA, et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012; 47(6): Please contact the MS Trust Information Team if you would like any further information about reference sources used in the production of this publication. Further information From the MS Trust Stem cells and MS: where are we now? In Open Door March 2015 pages Is stem cell therapy right for my MS? (blog available at MS Explained From stem cell organisations EuroStemCell has a factsheet on Multiple sclerosis: how could stem cells help? EuroStemCell is an independent organisation funded by the European Union. The Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation has produced a patient advice statement: General information for patients, families and carers considering HSCT for a severe autoimmune disease: A position statement from the EBMT Working Party for Autoimmune Diseases and JACIE EuroStemCell answers FAQs (frequently asked questions) about stem cells and regenerative medicine International Society for Stem Cell Research answers Stem cell FAQs (frequently asked questions) about stem cells and stem cell treatments International Society for Stem Cell Research has a website that takes a closer look at stem cells UK Stem Cell Foundation is a charity focussing on stem cell research 24