In the past month, two new treatments for multiple sclerosis have hit the headlines. One STEM cell-based therapy is being touted as a ‘game changer’ in many reports and the other drug-based approach, published in The Lancet, looks very promising.
What is multiple sclerosis?
Multiple sclerosis (MS) is an immune-mediated disease involving an attack on certain cells and structures within the central nervous system (CNS) by the body’s own immune system. The body mistakenly attacks myelin – a fatty coating insulating nerve cells – which affects the nerves’ ability to conduct signals. Symptoms include:
- Balance and coordination issues
- Fatigue
- Numbness and tingling in parts of the body
It affects around 2.5 million people worldwide and can be divided into two varieties:
- Relapse-remitting MS – the more common type, typified by periods of worsening symptoms (relapses) followed by periods of remission. After many years, some sufferers will develop secondary progressive MS. This is characterised by a gradual worsening of symptoms.
- Primary progressive MS – the less common type where the symptoms gradually worsen over time.
The aetiology of MS is unknown, though it is believed to be multifactorial, with environmental, immunological and genetic factors thought to be at play, however direct links are muddy.
The ‘game changer’ was announced at the annual meeting of the European Society for Bone and Marrow Transplantation by Dr Richard Burt.
It uses haematopoietic stem cell transplantation (HSCT) to create immune cells without the memory of MS, meaning they shouldn’t attack the body’s CNS.
This is a risky approach and involves a few steps. Firstly, the patient goes through a course of chemotherapy to encourage the production of bone marrow and fresh stem cells and their subsequent circulation through the blood. The cells are then collected before the patient undergoes another extensive cocktail of chemotherapies to wipe out their established immune system.
The theory here is that older immune cells are sensitised to myelin and ‘teach’ the younger immune cells to attack the myelin sheath around the nerves. These older immune cells not only attack the myelin directly, but they release chemicals that damage the nerve cells themselves.
Once the old immune response has been removed, the young stem cells collected earlier in the process are introduced back into the body. This in effect is a reboot as the younger cells had not been taught to attack the myelin. The immune system essentially reverts to a time before MS. We don’t know whether the nerve tissue can recover yet, however at least further damage to the CNS is unlikely.
Each stage in this procedure carries inherent risk. Between one and two people per hundred who have undergone HSCT have died as a result. Chemotherapy can lead to fatigue and hair loss while stripping away the immune system leaves the patient at risk of infection. As such, they require isolation under specialist conditions.
HSCT is only suitable for those with the relapse-remitting form of the disease and disease modifying therapies need to have failed for this avenue to be pursued.
What about those with other forms of MS? A large clinical trial has found that a drug called siponimod has reduced the rate of disability progression in secondary progressive MS.
In a study peer-reviewed and published in The Lancet, the rate of disease and disability progression has been shown to decrease compared with a placebo group. The study involved 1645 patients, with 1099 in the siponimod group and 546 in the placebo group. The trial took place in 292 hospital clinics and MS centres in 31 countries.
Siponimod works by trapping types of immune cells (B and T cells) in the body’s lymph nodes. This stops the immune cells from attacking and further damaging the myelin in the CNS.
The patient’s disability was measured every three months and confirmed if the level of disability remains for another three months.
The trial found that 32% of the placebo group experienced confirmed disability progression (CDB), whereas only 26% of the siponimod group did – this works out as a 21% relative risk reduction, which is certainly not insignificant.
The study was funded by Novartis, who are in plans to apply for a European licence for the treatment. If this proves successful, siponimod will be judged for cost effectiveness as an NHS treatment.
What does the future hold?
It is worth noting here that these treatments are targeted at different types of MS. The HSCT treatment is targeted towards relapse-remitting MS, whilst the siponimod drug approach is for secondary progressive MS.
One of the therapies has been published, the siponimod therapy having been peer-reviewed in The Lancet, whilst the HSCT has only been reported in the news and at a conference. It is due to be published in May this year so further details may be unveiled, but the exact methodologies and results are as yet unclear, though all reports sound extremely promising. What we do know is, for now at least, HSCT is expensive, costing around £30,000.
Both methodologies require development before we will see them as standard practice. For sufferers of MS, it is good to see what is being developed and that emphasis is being placed on the different forms of the disease.