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Multiple sclerosis (MS) is a disease in which the body’s immune system mistakenly attacks the protective myelin coating on the nerve cells in the brain and the spinal cord. In most people, the initial stages of their MS are characterised by exacerbations or “relapses” of disease, that involve worsening of symptoms such as limb weakness, blurred painful vision, numbness, or pins and needles. Between relapses the symptoms may dissipate completely, however permanent neurological deficits often remain leading to accumulation of disability. The triggers and mechanisms involved in MS relapse are not clear. Steroids are generally used to treat MS relapses, but these have many side effects, and better treatment options for relapse are needed.
In this 3-year project, Dr Mastura Monif’s team examined the role of a specific immune cell called the monocyte in MS relapses. Monocytes are found in the blood but can enter the brain and are found in large numbers within the injured areas of the brain and spinal cord in MS. There is accumulating evidence that activation of these immune cells can contribute to worsening of MS. In particular, the project focused on a protein, the P2X7 receptor (P2X7R) which is found on the surface of monocytes.
Dr Monif and her team have recruited participants who were having acute MS relapses and isolated monocytes from their blood samples. She found that P2X7R is more active in monocytes at the time of an MS relapse, and the number of monocytes in the blood was lower during a relapse compared to when in remission.
Other types of white blood cells (e.g. lymphocytes and neutrophils) were also analysed. The total number of lymphocytes decreased during a relapse compared to when in remission in people with active lesions”. The number of neutrophils circulating in the blood was also higher in people who have active lesions at the same time as an MS relapse.
Lower numbers of lymphocytes and higher numbers of neutrophils circulating in the blood, people being older, and longer duration of MS were associated with a greater level of disability during a relapse. Lower levels of lymphocytes were associated with the presence of an active lesion. Higher numbers of monocytes circulating in the bloodstream were associated with active lesions.
The levels of P2X7R and neurofilament light chain (which rises in the blood and cerebrospinal fluid when nerve cells are damaged) were similar in the blood of people with MS, regardless of whether they were experiencing a relapse or were in remission. However, P2X7R was more active in people with MS who experienced a relapse compared to people with MS in remission.
Monocytes from people with MS experiencing a relapse produced substantially more of some of the molecules that activate and control immune responses compared to monocytes from people with MS in remission, but less of other types of immune molecules.
Dr Monif has collected a biobank of monocytes and blood from people with MS in relapse versus remission which will be used for future studies into immune proteins and MS. The findings of Dr Monif’s studies show that further research on P2X7R and its role in MS relapse are needed. The ultimate aim of this work is to develop therapies targeting P2X7R that could potentially halt MS relapse.
Updated 31 March 2024
$220,000
2021
3 years
Past project
