The Science

Relaxin; background

Underlying the need for effective and well tolerated therapeutics to increase compliance in treating relapses in Multiple Sclerosis, prompted our investigation of the anti-inflammatory immune-modifying pregnancy hormone relaxin as a novel pathway.

A spontaneous remission of symptoms in the later stages of pregnancy has been well characterized in subjects with MS, (Lorenzi and Ford, 2002). These remissions are thought to be due to the production of pregnancy hormones. One such pregnancy factor is Relaxin, a member of the relaxin peptide superfamily (Bathgate et al, 2013) which is also up regulated in the later stages of pregnancy (Goldsmith and Voskuhl, 2009). Relaxin is pleiotropic in nature, acting as an agonist for the glucocorticoid receptor (GCR, Dschietzig et al, 2004) and the relaxin family peptide receptors 1 and 2 (RXFP1 and RXFP2, Bathgate et al, 2013). Through these receptors RLN can modulate the immune system by suppressing cell adhesion molecules (Bani et al, 2003), increasing cyclic adenosine monophosphate (Nguyen and Dessauer, 2005), regulating differential expression of matrix metalloproteinases (Mu et al, 2010), regulating cytokine and chemokine receptor (CCR) expression (Bathgate 2013) and inhibit cell-mediated pro-inflammatory activity by stimulation of the peroxisome proliferatoractivated receptor gamma (PPARγ; Singh and Bennet, 2010) which has neuroprotective effects (Gray et al, 2012). Through these diverse actions, RLN could have a potential to modulate the clinical symptoms of MS, be neuroprotective and promote remyelination.

The use of glucocorticoid agonists in treating acute attacks of multiple sclerosis is well established. Relaxin, a member of the insulin super family is a pleiotropic hormone capable of influencing multiple pathways which include the glucocorticoid receptor and relaxin family peptide receptors 1 and 2. In addition to the action of relaxin on the glucocorticoid receptor, activation of the relaxin receptors have additional anti-inflammatory and immuno-modulating effects.

Our study has shown that relaxin significantly reduced the clinical signs of disease, decreased mRNA expression of pro-inflammatory cytokines and chemokine receptors. Treatment also lead to a decrease in lesion load and size and macrophage infiltration, preserved myelin and neurofilaments, reduced gliosis and promoted remyelination.