The permanent symptoms of MS develop when nerve cells are destroyed. Protecting nerve cells from destruction, or neuroprotection, is therefore an important target of research.
Multiple sclerosis causes nerve damage through inflammation which results in demyelination. This is when the nerves of the central nervous system 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.
The current disease modifying drugs focus on preventing the inflammation and subsequent demyelination in relapsing remitting MS, but they are not effective for treating progressive forms of MS. However, 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 particular 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.
New research directions
Researchers looking at exactly how nerve cells die have identified a number of opportunities where a new drug could operate to prevent nerve cell death.
Glutamate is one of the chemicals involved in transmitting messages from nerve cell to nerve cell. Excessive glutamate around the nerve cell can lead to the loss of nerve fibres and some research is looking at ways to control this.
- 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 MRI changes.
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, though the results did not differ from placebo.
- 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 retina than people taking a placebo.
Existing drugs re-evaluated
Drugs that have been used in other conditions are currently being investigated for their neuroprotective effect in MS:
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.
Diet and antioxidants
Oxidative stress occurs as a result of a mismatch between cellular processes that produce reactive oxygen in the body, and those that mop it up and convert it into other substances. Ideally, these processes are kept in balance, as too much reactive oxygen around nerve cells damages them. In MS, oxidative stress occurs as a result of inflammation, and so researchers are looking at antioxidants as possible candidates for neuroprotection.
Antioxidant substances from the diet, such as polyphenols from green tea, red wine or olive oil, and vitamins C and E are being studied in relation to MS. It is possible that the supposed benefits of dietary modification in MS 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, MSC migrate to places where inflammation and damage are occurring and seem, in studies of animals, 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.
- Journal of Neurological Sciences 2008;265(1-2):21-25. Summary Neuroprotection and repair.
- Current Pharmaceutical Design 2012;18(29):4471-4474. Summary Neurodegeneration and neuroprotection in multiple sclerosis.
- Trends in Neuroscience 2010;33(3):140-152. Summary Neuroprotection, regeneration and immunomodulation: broadening the therapeutic repertoire in multiple sclerosis.
- Current Opinion in Neurology 2006;19(3):255-259. Summary Neuroprotection in multiple sclerosis: therapeutic strategies and clinical trial design.
- Journal of Neurological Science 2005;233(1-2):113-115. Summary Glutamate inhibition in MS: the neuroprotective properties of riluzole.
- Lancet Neurology 2010;9(7):681-688. Summary Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial.
- Neurotherapeutics. 2016 Jan; 13(1): 58–69. Full article Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis
- J Neurol Sci. 2013 Oct 15; 333(0): 43–49. Full article Mesenchymal Stem Cell Transplantation in Multiple Sclerosis