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Recent developments in MS research

Multiplesclerosis (MS) research is highly active, as shown by the proliferation of communications  in national and international congresses as well as the number of publications concerning the disease. The purpose of this article is to summarise a number of recent developments in this area.
Genetic factors
A recent German genetic study has identified several new genetic variants, of which one is close to a gene known as SHMT1, which intervenes in chemical changes to our DNA. This is an important discovery, which confirms the crucial connection between genetic susceptibility and environmental factors.
In Belgium, An Goris’s team has shown that such genetic variants are correlated with certain of the disease’s clinical characteristics, such as the annual relapse rate and the earlier occurrence of subsequent relapses further to the inception of the disease.
This year, for the first time, a gene (NR1H3) was identified as being involved in the familial forms of progressive multiple sclerosis. A study of the functions of this gene may supply further therapeutic approaches in the future.

It has been known for a long time that the immune response of 95% of MS patients is detectable in the cerebrospinal fluid in the form of specific oligoclonal immunoglobulin G. A recent study has shown that a number of auto-antigens were intracellular proteins, indicating that immune response in MS is in part secondary to cell destruction.
One recent and prestigious paper shows that miRNAs are involved in the dysfunction of regulatory T cells. MiRNAs are small molecules that play a crucial role in many biological processes. In the future, they may be used as biomarkers and even as therapeutic agents.

Treatments currently under evaluation

  • On animal models: In animals, treatment with an anti-semaphorin antibody attenuates experimental autoimmune encephalomyelitis (an animal model fairly close to MS) and stimulates  remyelination as well as the migration of oligodendrocyte (the cells that produce myelin) precursors to lesions. An antibody (glunomab) blocks a specific protein on the internal surface of the brain’s blood vessels and prevents the migration of blood immune cells through the vessel walls, resulting in a less severe  disease in animals. These vessel walls constitute the blood-brain barrier and are thus made less permeable.

  • Neuroprotective and remyelinating therapies. In the area of research on remyelinating therapies, two clinical studies on antihistaminic molecules (clemastine and GSK239512) are under way. In vitro, clemastine can induce the differentiation of oligodendrocyte precursor cells.The potentially neuroprotective effects of phenytoin, an anti-seizure medication, has been studied in optic neuropathy. The results showed that there was a protective effect of approximately 30% on the thickness of the peripheral retinal nerve fibres, opening the way to future studies with  possible therapeutic applications.

New magnetic resonance image (MRI)analysis techniques are currently under review, for instance, spectral MRI analysis enables to assess the degree of (de)myelination of multifocal MS lesions  in the brain.
Diffusion tensor imaging (DTI) is an MRI technique which enables nerve fibres to be tractographically assessed in order to analyse intracerebral connectivity. This is a fast-expanding technique correlated with the progression of invalidity, cognitive disturbances or fatigue in MS patients.
One recent study correlated alterations in connectivity with the accumulation of intracerebral iron deposits. This observation is consistent with the progression mechanisms of MS, which involve the accumulation of iron in the malfunction of the energy manufacture of neural cells (at mitochondrial level), causing axonal degeneration.

Importance of the registries
The international MSBase Registry, in which over 30,000 MS patients are participating, regularly publishes large-scale studies and makes a significant contribution to the characterisation of MS epidemiology and of its long-term evolution. The Register also enables indirect comparisons to be made between the many treatments currently available. In Belgium, the Charcot Foundation is supporting the creation of a similar register for Belgian patients known as BELTRIMS.

To conclude, MS research is in a state of perpetual flux and there is hope that it will significantly contribute to changing the understanding, diagnosis and treatment of the disease.

Professor Vincent van Pesch
Clinique Universitaire Saint Luc , Brussels