Stem cell
 
 
 
 

therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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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 12 
5. Is stem cell treatment available for MS? 16 
6. Key considerations 21 
7. 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.

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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.

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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.

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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).

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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
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.

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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
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
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
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
 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.

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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 www.jacie.org. 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.

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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
 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
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
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;
NCT00273364) is recruiting in Sheffield. It is part of a multi-centre trial

16
 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 www.clinicaltrials.gov. 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 (www.clinicaltrials.gov) but none of them
need more participants. They are included here for information only. The trials are:

 MSCIMS (Mesenchymal Stem Cells in Multiple Sclerosis; NCT00395200 ),

based in Cambridge and London which has already completed.

 STREAMS (Stem Cells in Rapidly Evolving Active Multiple Sclerosis;

NCT01606215) 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; NCT01815632) 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 01932593) 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 (www.clinicaltrials.gov) using the search
term “multiple sclerosis AND stem cells” and then using the map function to focus
in to the UK.

17
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
 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

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 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.

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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.

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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 www.jacie.org.
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

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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.

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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):275-284.
 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): 95-107.
 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):770-790.

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 16-17
Is stem cell therapy right for my MS? (blog available at www.mstrust.org.uk)
MS Explained

From stem cell organisations

EuroStemCell www.eurostemcell.org/ 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 www.ebmt.org 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 www.eurostemcell.org/ answers FAQs (frequently asked
questions) about stem cells and regenerative medicine
International Society for Stem Cell Research www.isscr.org/ answers Stem
cell FAQs (frequently asked questions) about stem cells and stem cell treatments
International Society for Stem Cell Research www.closerlookatstemcells.org/
has a website that takes a closer look at stem cells
UK Stem Cell Foundation http://www.ukscf.org/ is a charity focussing on stem
cell research

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