Are stem cells really a game-changer in MS therapy?

Posted on 27 February 2019 in Stem cell therapy

Today, my quick Google search for ‘stem cell therapy’ gave me 435 million results within 0.71 seconds, and the number of ‘clinics’ offering this treatment for a huge range of diseases and injuries is staggering!

Why?

The hope generated by the great medical potential of stem cells has led to clinics worldwide claiming to have the “cure” for almost every imaginable condition. The reality is that, currently, only a few stem cell-based treatments have been rigorously tested and scientifically proven as both safe and effective.

Haematopoietic (blood) stem cell transplantation (HSCT) has evolved over a period of more than 50 years to treat a wide range of conditions and is now a routine part of blood disorders practice. As of 2018, the European Registry holds data on over half a million patients who have had HSCT. There were only 1,228 PwMS on the Registry in June 2018.

Stem cell treatment for PwMS has understandably generated a great deal of interest and hope but with this comes the controversies and fictions! I want to help clear things up a bit for you.

Image result for stem cell multiple sclerosis
Fig 1: Infographic by the MS Society of the basic process of AHSCT stem cell procedure

The main stem cell treatment currently available to treat MS is the Autologous Haematopoietic (blood) stem cell transplantation (AHSCT – see fig 1). The patient’s own stem cells are harvested and stored temporarily while high doses of chemotherapy and biologics are used to destroy the “faulty” immune system. The “new” immune system is regenerated from the infused stem cells.

The infused stem cells will not repair the damage in the brain and spinal cord already caused by MS but will speed recovery of the blood cells needed to re-boot the immune system.

The highly efficacious disease-modifying treatments (HE DMTs), also known as  immune reconstitution therapies (including alemtuzumab and cladribine) can also re-boot the immune system and are around as effective as AHSCT.

How effective is AHSCT in MS?

It can be extremely effective; especially in highly active MS, but decisions must look at the benefit versus the risk.

Figure 2 gives a simple picture of the relative efficacy and risks compared to other DMTs.

Fig 2: Graph showing the relative effectiveness and risk of different DMTs
Courtesy of Prof A. Coles, Cambridge

The diagram shows how effective the treatment is on the Y-axis while the risks, which include side effects and  difficulties in giving the treatment, are on the X-axis.

There is an increasing body of evidence that AHSCT improves all measured MS outcomes. This includes the impact MS is having on a person as recorded by MRI, clinical relapses, accumulation of disability, and quality of life when compared to patients whose active MS is not controlled with a standard therapy.

To explore the eligibility criteria and risks of AHSCT, look at the collapsed sections below.

Is It a miraculous MS cure?

AHSCT is a well-known cure for some serious blood conditions but would not completely satisfy the requirements for “ideal MS cure” mentioned in a previous article.

There are media reports that some PwMS experienced a ‘miraculous cure’ with anecdotes of those reliant on wheelchairs dancing, and blind people re-gaining sight. This outcome is certainly not seen in the majority of patients who received this treatment when we look at the scientific reports and studies.

In our clinic, we discuss the option of stem cell therapy as part of a holistic personalised treatment plan and advise as to whether this type of treatment is right for you. 

AHSCT is considered a major procedure and is linked to very serious adverse risks including morbidity and mortality (see fig 3). Compared to any other known MS treatment this is significant, and is the main reason that AHSCT is not used more widely.

Fig 3: The top adverse risks associated with AHSCT

Most MSologists currently agree that the best candidates for treatment would be young people with Relapsing MS who failed a trial of one or more HE DMTs. There are actually very few people this applies to now given the increasing availability and efficacy of DMTs.

Some DMTs can compete with AHSCT’s efficacy with less risk and easier administration (fig 2). These DMTs have been confirmed as effective in sizable populations using controlled and blind trials whereas trials in AHSCT involve relatively small numbers and are mostly either un-controlled or the control does not include HE DMT. (It is difficult to carry out blind trials in AHSCT)

The current eligibility guidelines are felt to strike a reasonable balance between efficacy and risk. These guidelines are followed by  most experienced and regulated stem cell centres.

Eligibility guidelines are:

  1. Evidence for active inflammation
    • frequent relapses
    • and/or new or active lesions on MRI
  2. Preferably younger people
  3. Short disease duration (less than 15 years)
  4. Ability to walk (EDSS score of less than 6.5)
  5. Good general condition

Private clinics, unsurprisingly, are often less specific in their requirements. Others perform “stem cell” treatments which are not recognised to be of any potential benefit. Standardisation and proper regulation are major issues with many clinics.

Critics of AHSCT believe that there is no convincing evidence that it is superior to the DMT Alemtuzumab to warrant the potential high risks associated with it. However, enthusiasts are often willing to take the risk in hopes of the ‘miraculous cure’ that very few people have experienced. Alemtuzumab does have potential serious side effects, too.

It is generally accepted that the data on disability improvement is better for AHSCT when compared to other DMTs although there is no clear evidence of why. Improvements in disability could be simply due to internal bodily repair encouraged by suppressing active inflammation in the brain and spinal cord.

Current data suggests that the effect of AHSCT in progressive MS (secondary and primary) is moderate at best, and at the moment should only be used for clinical trials.

A recent 2019 JAMA publication has been widely shared and quoted. It supports the previous data on better outcomes in disability (EDSS) improvement with stem cell procedures compared to other DMTs. The study, looking at 55 people with RRMS on stem cells, with an average follow-up of 2 years, was preliminary, open-label (not blinded) and the comparison control group did not include patients on Alemtuzumab – the closest DMT in terms of similar efficacy. There was no death in this cohort and adverse events were less troublesome. It may be that the evidence gathered is very useful, but taken on its own gives a skewed picture of the outcomes of stem cell procedures in MS.

A recent risk-adapted approach suggests using a lower-intensity chemotherapy regimen for patients who have inflammatory, but less aggressive, relapsing MS. This scenario would only use higher-intensity regimens, which are associated with more extreme adverse events, for those with a more aggressive form of MS.

If the risks of AHSCT procedures can be reduced even more without compromising their long-term benefits, AHSCT could be  used for PwMS earlier – potentially as a first-line therapy. We need data from trials comparing AHSCT to HE DMTs to support this approach.

There are two major centres performing AHSCT for PwMS in London and Sheffield. Both accept both NHS and private patients and are involved in research. These centres have excellent reputations, distinguished experience and are heavily regulated.

In our clinic, we discuss the option of stem cell therapy as part of a holistic personalised treatment plan and advise as to whether this type of treatment is right for you.

What about the cost?

The total cost of AHSCT might be favourable compared to current HE DMTs by NHS standards. This is believed to be a major factor encouraging the NHS to support a large comparative trial, and if the results are positive for AHSCT, this might pave the way for wider and earlier use.

For private patients in the UK, the current cost of the procedure is more than £60,000.00.

If you are considering going abroad for this treatment, I recommend carefully reading the advice on the MS Trust website.

My view

My personal view is that AHSCT is a real game-changer for those few people with MS who  have an aggressive form of MS which is not responding to HE DMT.

  • I think that the benefit-risk ratio for most PwMS is not in favour of AHSCT at this point in time, although the data for improvement of disability is impressive.
  • The wishes of a well-informed person with MS should always be part of a shared-decision-making process with their wider MS team.
  • Stem cell therapy should be part of a holistic multi-professional management approach to give PwMS the best possible quality of life. This includes management of MS symptoms, neuro-rehab issues, cognition and psychological elements, co-morbidities and lifestyle changes. A small contribution from each can add positively to the quality of life for those living with all types of MS and degrees of disability.

What about future perspectives

Stem cell researchers struggle with funding and recruiting PwMS into trials and cannot compete with the big pharma investment in DMT research. It is likely that we will have more DMTs that can re-boot the immune system with less risks before stem cell research will deliver the data and safer techniques needed to support its wider use, unless a big player enters the race, like the NHS!

Dr Adnan Al-Araji
Consultant MS Neurologist

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