Protecting nerve cells from destruction is called neuroprotection. This is an important goal for current research.
Multiple sclerosis causes nerve damage through inflammation which results in demyelination. This is when the nerves in the brain and spinal cord are attacked and their protective myelin sheath is stripped away. The nerve fibres are then exposed to the chemicals produced by inflammation, and nerve cell death (neurodegeneration) is then likely to occur.
Myelin can be regrown under some circumstances, but the myelin repair may not always be effective. If the myelin is not regrown then the nerve cells will subsequently die. Once nerve cells die they are not usually repaired or replaced. This can lead to MS progression and irreversible MS symptoms, but not all ongoing MS symptoms will be caused by nerve cell death.
The current disease modifying drugs are given to prevent the inflammation and subsequent demyelination in relapsing remitting MS, but they are not usually effective for treating progressive forms of MS. Researchers working on neuroprotection aim to find ways in which nerve cells can be protected from inflammation and damage. The hope is that the destruction of nerve cells - and thus further permanent problems - can be lessened or prevented.
Research in this area is at a relatively early stage and these studies are exploring the potential of neuroprotection as a strategy, as well as the possibility of making effective drugs available to people with MS. Neuroprotective drugs will not be able to reverse progression or restore lost function. However, if suitable drugs can be developed, it is hoped that this will mean that the progression of multiple sclerosis can be significantly slowed down - something that is not possible with existing medication.
To work out how to protect nerve cells, researchers have studied what causes nerve cells to die. This approach has identified opportunities where a new drug could prevent nerve cell death.
Glutamate is one of the chemicals involved in transmitting messages from nerve cell to nerve cell. If excessive glutamate builds up around the nerve cell, it can lead to nerve cell damage. Some research is looking at ways to control glutamate.
- Riluzole is a glutamate inhibitor that is used in the treatment of amyotrophic lateral sclerosis (ALS), a form of motor neurone disease. A small study involving 16 people with primary progressive multiple sclerosis did not show any definite effect of riluzole on clinical disability, although the participants showed less degenerative changes on their MRI scans.
Inflammation leads to the increase in levels of nitric oxide and sodium, both of which can damage nerve cells. Research is underway to examine the effect of blocking these chemicals.
- Lamotrigine is a sodium channel blocker sometimes used to treat pain in MS that has been studied as a potential neuroprotective drug. There is not yet any conclusive evidence that it is effective in preventing nerve cell death.
- Phenytoin is a sodium channel blocker used to treat epilepsy. A study in people with optic neuritis found that people who had been treated with phenytoin showed less damage to nerve cells in the eye than people taking a placebo.
Research into remyelination aims to find treatments that can protect nerves by rebuilding the myelin layer. This approach is discussed by Dr Nick Cunliffe in the film below.
Drugs that have been used in other conditions are currently being investigated for their neuroprotective effect in MS:
Some recently developed DMDs, such as ocrelizumab and siponimod have been shown to have a neuroprotective effect alongside their effect on relapses.
Also, studies have identified a neuroprotective effect from statins, and studies into the effect of simvastatin on SPMS are under way.
- Amiloride has shown signs of limiting damage to nerves in a small study of people with primary progressive MS, though more research is needed.
- Ibudilast has been studied in people with relapsing remitting MS to see if the drug would have a neuroprotective effect.
- Eliprodil has been investigated as a treatment for Parkinson's disease. There have been very early laboratory trials in MS.
- Cannabis was studied in a trail called CUPID that showed it was no better at reducing progression than placebo.
Amiloride, ibudilast and riluzole have been studied by the large MS-SMART trial looking for a neuroprotective effect in people with secondary progressive MS. The results were announced in October 2018, and no significant benefit was found from any of these drugs for people with progressive MS.
Chemical processes in your cells can produce reactive oxygen in your body. Other processes mop up the reactive oxygen and convert it into other substances. Ideally, these processes are kept in balance, as too much reactive oxygen around nerve cells damages them. This is called oxidative stress. In MS, oxidative stress occurs as a result of inflammation, and so researchers are looking at antioxidants as possible treatments for neuroprotection.
Antioxidant substances from the diet, include polyphenols from green tea, red wine or olive oil, and vitamins C and E. Many of these substances are being studied in relation to MS. It is possible that the some of the benefits seen when people with MS make healthy changes to their diets comes from the neuroprotective effect of these substances.
Mesynchymal stem cells (MSC) harvested from bone marrow are able to change into a variety of other cell types. Once in the body, these cells migrate to places where inflammation and damage are occurring. In some studies in animals, these cells appear to be able to repair the damage.
Preliminary studies in people with MS, both RRMS and SPMS, showed that the process was reasonably safe, but there has not yet been long term follow-up to see if there was a significant neuroprotective effect.
It is important to stress that this process is not the same as AHSCT, which is used to reboot the entire immune system in the hope of producing a long-term remission of MS symptoms. MSC treatment, if it becomes a mainstream therapy, is likely to need repeated injections of stem cells to treat ongoing damage.
