The recent announcement about the use of stem cells to treat a form of multiple sclerosis (MS), together with early results from the BrainStorm stem cell amyotrophic lateral sclerosis (ALS) clinical trial in Israel have raised the profile of stem cells as a possible treatment for motor neurone disease.
Stem cells are unspecialised cells in the body which do not yet perform a particular function. They can renew themselves and have the ability to give rise to different types of cell, including nerve cells (motor neurones and the surrounding support cells).
Both the ALS/MND study (ALS is a type of motor neurone disease) and the MS study used stem cells found in bone marrow taken from the patient, and then given back to the same patient later on in the process. The MND study gave a new use to the bone marrow stem cells, whereas in the MS study ‘corrupt/damaged’ stem cells were replaced with a new healthier set.
Below we look at both trials in more detail and describe what they mean for people living with MND.
BrainStorm stem cell clinical trial results
Results from the phase 1/2 and phase 2a parts of this trial were published last week in the journal JAMA Neurology.
Phase 1/2 and 2a are the earliest stages of the clinical trials process. They are focussed on establishing the safety of a potential treatment, rather than if it shows any possible clinical benefit.
How does the treatment work?
In these trials one type of stem cells found in bone marrow (called mesenchymal stem cells) were given to participants via injections. Nerve-nourishing (neurotrophic) factors were also given with the stem cells. The idea is that the stem cells would deliver higher levels of the nerve-nourishing factors to the usually inaccessible brain and spinal cord. These nerve-nourishing factors might help extend the survival of motor neurones.
What did the trials involve?
The Phase 1/2 study (study 1) involved 12 people. Six people with early stage ALS received stem cell injections into arm muscle, and six with a more advanced form of ALS had injections of stem cells into the spinal cord fluid.
In the Phase 2a study (study 2), 14 people with early stage ALS had stem cell injections into both the muscle and spinal cord.
What were the results?
The two studies showed this type of stem cell was safe when injected into arm muscle or into the spinal cord, with no serious side effects. Results from the first study informed the design of the second study.
The studies did not fully record the clinical treatment effects of the stem cell injections, though ALS functional rating scale (ALSFRS-R) scores and forced vital capacity (FVC) measures were recorded in the second study. Patients were monitored for three months prior to treatment and six months following treatment.
Progression in ALSFRS-R scores and FVC were reduced, with 13 out of the 14 people from study 2 defined as ‘responders’ to the treatment. This meant that according to one of the two measures they had a trend towards a slower progression rate in their disease after treatment compared to before they had it.
What do these results mean?
These are very early stage studies, on a relatively small number of people. Also these trials did not have any placebo-controlled set of participants to compare results to. Those reasons mean we cannot read too much into these results.
That the safety of this particular form of stem cell treatment is beginning to be established is a positive step. The two trials will help researchers work out where it might be best to inject stem cells (spinal cord versus into muscle). This study suggests that spinal cord might be the better option.
A larger third study (Phase 2) of the BrainStorm treatment trial is underway. This time it will be placebo-controlled and double-blind (meaning neither doctors nor patients will know which treatment they received). This study is not recruiting people to take part.
Using stem cells as a therapy for MND is still an experimental and unproven treatment, and further research is needed before we can say if they could be a successful treatment for slowing MND progression.
MS stem cell trial
An ongoing study, recently reported on BBC Panorama, has looked at the use of another type of stem cell found in bone marrow (called haematopoietic stem cells) as a treatment for the remitting/relapsing form of MS. Early results have shown a reversal in the symptoms of several people who received this treatment.
How does it work?
Patients had the ‘corrupt/damaged’ stem cells retrieved from their bone marrow followed by high-dose chemotherapy to wipe out their immune system. Their own stem cells, now no longer corrupt, were re-injected to help re-boot the immune system, and prevent further damage happening to the brain and spinal cord.
Can the same or similar process be used for treating MND?
We need to be cautious about translating results from treatment trials in one neurodegenerative disease across to another.
The role of immune system and its relationship to neurodegeneration in MND is not fully understood, so we do not know if re-booting the whole immune system in someone with MND, and then giving them stem cell therapy, would work like it appears to have done in people with MS.
Current stem cell trials for treating MND do not use chemotherapy as part of the treatment course, and are not using the haemotopoietic type of stem cells.