Multiple sclerosis and stem cell transplants: benefits versus risks

Multiple sclerosis, or MS, is a complex neurological and autoimmune disease whereby a patient’s immune cells, for unknown reasons, begin to attack the protective layer surrounding the nerves in the brain and spinal cord. This protective sheath is known as myelin. When myelin degenerates as a result of this autoimmune-mediated damage, the nerves are exposed and therefore prone to damage. This results in progressive disability and can significantly reduce a patient’s quality of life.

Two women have recently returned to Scotland after travelling to Russia to receive stem cell therapy for their MS, a treatment which is not widely available in the UK. Stem cells are the cells in the body from which all other cells are formed, and there are different ones for the various cell types of the body. They underwent what is known as a haematopoietic stem cell transplantation (HSCT). A haematopoietic stem cell is one that gives rise to all the blood cells, including the body’s immune cells. 

This type of treatment regimen is quite aggressive, so only those considered fit enough to undergo it are eligible. First, the stem cells are taken from the patient’s own blood or bone marrow. They then have to receive chemotherapy to wipe out their existing immune system. This is necessary to provide a blank canvas for the patient’s blood stem cells that are then transplanted back in to form a new immune system, the goal being that it will hopefully no longer attack the patient’s myelin.
HSCT can stabilise the disease and significantly improve disability for some MS patients, which can be life-changing.

However, the eligibility criteria in the UK is very strict due to the risks involved in the procedure. Suppression of the immune system can leave patients extremely vulnerable to infections, because the body is unable to fight off even the most harmless of infections as it normally would. The recovery is long and arduous as a result, with patients having to strictly limit their interactions with other people for several months – much like we are all doing currently to avoid COVID-19 transmission. The side effects of high dose chemotherapy, such as nausea and hair loss, can also be very unpleasant, and infertility can be an additional concern. One of the greatest long-term concerns is the possibility that patients could develop other autoimmune diseases, such as autoimmune thyroiditis, following transplantation. For these reasons, this type of stem cell therapy is currently deemed too high risk as a first line therapy for MS in the UK, and is only recommended for patients who have severe disease and for whom other treatments haven’t worked. 

While HSCT has been successful in treating leukaemia, MS is different to other diseases in that its root cause is multifactorial – it is not just a disease of the brain and spinal cord, it is also an autoimmune disease. This makes it more difficult for researchers to understand, and therefore treat it. The main drawback of blood stem cell therapy is that it is designed to reboot the immune system only. This can be effective in preventing further damage to the patient’s nerves, however it does not target the brain, nor repair damage that has already occurred. 

For this to be possible, a different type of stem cell, known as a neural stem cell, is required. These stem cells are found in the brain, not the blood or bone marrow, and they can be used to generate oligodendrocytes, the cells that make the protective myelin sheath. This approach, aiming to replace damaged oligodendrocytes, is at an earlier experimental stage at the moment. In Glasgow, the Edgar group have recently shown that neural stem cell transplants can restore myelin production in diseased mouse brains with myelin loss. Meanwhile, researchers in the Goldman group in New York have used another kind of stem cell called induced pluripotent stem cells (iPSCs), which are formed from human adult skin cells, and can then be used to produce the desired cell type, in this case oligodendrocytes. An advantage of neural stem cell therapy is that it would not require immunosuppression, and thus would not carry the associated risks. In addition, unlike HSCT, it could potentially be suitable for patients with the primary progressive form of MS, for which there are very few therapies.

However, this strategy is not as straight-forward as it seems. The Franklin lab at Cambridge have identified that ‘stiffness’ of the cell environment in the ageing rat brain can prevent progenitor cells from becoming mature, myelin-producing oligodendrocytes. This may be what is occurring in diseases like MS, preventing natural myelin repair and regeneration. Indeed, researchers at the University of Connecticut, in collaboration with the Williams group here in Edinburgh, have recently found that neural stem cells appear to be aged in patients with primary progressive MS. Thus, further studies to understand the changes that are occurring in the MS brain are required before they can progress to the clinic.

So, while HSCT can be life-changing for some MS patients, the benefits currently do not outweigh the risks to render it a viable front-line therapy for MS. In future, it may be that combining this type of therapy with those that target myelin regeneration could hold significant promise, and neural stem cell therapy could overtake HSCT as a new ‘wonder treatment’ suitable for all MS patients.

Written by Niamh McNamara and edited by Ailie McWhinnie.

Niamh’s thoughts:
MS is a multifaceted disease, and we still don’t yet completely understand its underlying cause. As I mentioned in the article, this makes it more difficult to develop treatments for it. However, given that MS is a neurodegenerative disease, novel therapies that target myelin regeneration and repair will be key in the fight against it. Eventually, combining these with those which halt damage, such as HSCT, could prove to be disease-modifying and thus, truly life-changing for MS patients.

Niamh is a PhD student in Tissue Repair, studying the roles of immune cells in brain development and infant brain injury. Find her on Twitter @niamh_mc_namara and LinkedIn @Niamh McNamara.