Marie Curie researcher investigates role of innate immune system in Multiple Sclerosis

Multiple Sclerosis (MS) is a neurological disease and has many faces that researchers still do not fully understand. It is believed to be an autoimmune disease, in which the immune system
reacts against components of the brain and spinal cord, recent research efforts have been looking into the possibility of exploiting the human body’s own immune system in MS therapy.

In the framework of the EU’s Marie Curie programme, Dr Bruno Gran of the University of Nottingham, UK, is investigating the use of the so-called innate immune system. As opposed to the adaptive
immune system, which is in charge of highly specific immune responses, the innate immune system is less specific. It is designed ‘to respond quickly to infectious agents such as bacteria and
viruses and to recognise patterns that are common to these infectious agents and start a rather potent and quick immune response that is eliminating these pathogens,’ Dr Gran explained in a
CORDIS News interview.

In principle, the innate immune system is able to recognise structural components shared by viruses, bacteria and other infectious agents with the help of Toll-like receptors (TRLs). The TRLs
as a type of pattern recognition receptor identify structurally conserved molecules derived from infectious agents once they have breached physical barriers such as the skin or intestinal
mucosa, and activate immune cell responses. ‘When this is initiated, the innate immune system also instructs the adaptive immune system to fine-tune a more specific response.’

So far, most recent MS research, including Dr Gran’s, has been focused on the adaptive immune system. ‘This is an initial investigation into the ability of the innate immune system to provoke
autoimmune reaction as opposed to the adaptive, from the point of view ofdisease mechanisms,’ he said. ‘If we then go on to the innate immune system, there are two aspects. One is the ability
to eliminate pathogens by provoking inflammatory immune responses that may then provoke damage to tissues. But also the ability to produce regulatory molecule like the Type 1 Interferons,
Interferon-beta and also Interferon-alpha. So, the concept here is that we use some of these molecules to treat MS.’

Currently, MS is treated with Interferons, most commonly Interferon-beta, a molecule that was initially discovered because of its antiviral properties but was later found to have an effect on
the entire immune system. However, the cost of producing Interferon-beta as a drug for injection are high, and the human immune system itself can produce large amounts of Interferon-beta, for
instance, during viral infections.

One year into the two-year project, Dr Gran has just started conducting experiments on mice using the animal model of MS, experimental autoimmune encephalomyelitis (EAE). In vitro experiments
on mouse and human cells, however, have already provided promising results: As Dr Gran had expected, toll-like receptor stimuli triggered the production of both pro-inflammatory cytokines, i.e.
signalling proteins and glycoproteins essential to cellular communication, and type 1 interferons.

Yet the aim of the project is to develop TLR agonists, substances that bind to TLRs and trigger a response in the cell, to a stage where they are ready for clinical testing in humans. This will
improve quality of life for people suffering from MS and reduce treatment costs at the same time.

However, there are a number of promising routes for MS treatment being explored at the moment. ‘We have had very significant advances in understanding and treatment in the last 15 years,’ Dr
Gran pointed out, adding that there is still a need to understand the genetic susceptibility better, as well as the interplay between genetics and environmental factors. ‘For example, viruses
can provoke disease relapses and recently, some very interesting data on the Epstein-Barr virus [a virus of the Herpes family] was published suggesting that it may be one of the pathogens
involved in disease susceptibility.’ In addition, Dr Gran predicts a gradually more customised, individualised treatment, as well as a greater role for stem cell research.

An estimated 500,000 patients in Europe alone suffer from MS. It destroys the insulating layer that surrounds the axons or nerve fibres of the neurons and thus hampers the transmission of
neural signals. MS is characterised by attacks of paralysis, loss of sensation and vision and genitor-urinary problems. It is the most frequent neurological disease in young adults and affects
twice as many women as men. The annual costs caused by MS in Europe amount to more than ?9 billion.

For further information, please visit:

Institute of Neuroscience at the University of Nottingham:
https://www.nottingham.ac.uk/neuroscience/

European Multiple Sclerosis Platform (EMSP):
https://www.ms-in-europe.org/