In many women with MS, disease activity is reduced during pregnancy. After pregnancy, there is often a return of disease activity. The improvement during pregnancy is thought to be due to alterations in the immune system of the mother. After the baby is born, these changes are reversed. The variations in the immune system during pregnancy are thought to be due to changes in hormone levels.
This project will study laboratory models of MS and look directly at changes in gene activity in the spinal cord. The study will first investigate changes that occur during pregnancy in the absence of disease and then move on to look at differences in MS model in different stages of pregnancy and afterward.
Understanding the molecular changes that underlie the effects of pregnancy on MS could lead to strategies to reproduce these effects as a therapy for multiple sclerosis.
Firstly Prof McCombe and colleagues studied the effect of pregnancy on the laboratory model of MS at different stages. They have demonstrated a marked difference in the occurrence and severity of disease across various stages of pregnancy and after the birth. The greatest benefit of pregnancy was seen during the late stages of pregnancy.
Prof McCombe then went on to characterise the gene activity levels during pregnancy and after birth in the spinal cord and brain compared with a non-pregnant state. They found changes in activity in a number of genes that could be relevant to MS, although the changes identified in pregnancy usually returned to pre-pregnancy levels after birth. Some genes remained at the pregnancy levels, suggesting that some genes may be switched off more permanently.
When gene activity was compared in cases of MS-like disease during pregnancy and in the absence of pregnancy, they found significant changes in the many immune and inflammatory molecules that are relevant to MS. Most excitingly, several genes which showed increased activity in the disease state compared to a normal non-pregnant state, were reduced during pregnancy, suggesting they may have a particularly important role.
This work has allowed Prof McCombe to predict which cellular systems might be important in controlling disease severity. The team is currently completing a more detailed analysis of the molecules and pathways involved. They are also interested in ‘splice variation’, which is a change in the size of proteins rather than the type of proteins that can occur in different situations and that may be due to the effects of hormones in pregnancy.
The long-term aim of this work is the identification of molecules that might provide novel therapeutic targets for treatment of MS.
Updated: 06 January, 2009