Nerve cells are similar to electric cables, and are covered in a protective coating called myelin. In multiple sclerosis, this sheath is lost, and current treatments are unlikely to promote myelin repair and regeneration. Regrowth of myelin is necessary to restore and maintain nerve functioning and to slow the progressive course of MS.
Dr Cate aims to identify new targets for treatments that enhance remyelination. It is known that particular chemicals inhibit myelin growth and repair in and around MS lesions. A protein called BMP is found in tissues near MS lesions and is thought to inhibit the myelin repair process. Dr Cate aims to decrease the activity of BMP in a laboratory model and determine if that results in increased myelin repair.
If successful, this new strategy could work alongside traditional MS therapies in order to increase myelin repair, prevent nerve cell damage and prevent functional decline in people with MS.
In MS the immune system attacks the fatty myelin sheath that is like an insulating covering of the nerve fibres. Damage to this sheath can prevent proper signalling between neurons, leading to the physical manifestations of MS.
Dr Cate found that a naturally occurring protein in the brain (BMP) can inhibit the cells (oligodendrocytes) responsible for the remyelination or recoating of the nerve cells. She found that this isn’t a direct effect of BMP on the oligodendrocytes but rather a by-product of BMP interacting with astrocytes, which are another type of support cell found in the central nervous system.
This important work is being carried on in the laboratory by a PhD student, Alistair Cole under the supervision of Dr Simon Murray and Dr Junhua Xiao. Alistair has continued to investigate the interaction of astrocytes and BMP, and how this interaction affects oligodendrocytes. After ruling out a number of other molecules, preliminary evidence indicates that the molecule BMP4 is involved in the replication of astrocytes and increasing their numbers. This in turn reduces the ability of oligodendrocyte precursor cells to mature, and then produce myelin. The team is now trying to identify the specific molecules secreted by the astrocytes that prevent oligodendrocyte maturation, whilst Alistair writes up his PhD thesis.
These findings are important in the efforts to develop new therapeutic strategies to complement immune targeted therapies by helping repair myelin and protect the vulnerable, exposed nerve fibres to prevent permanent axonal injury or loss and reverse the disease progression.
Updated: 23 June 2017
Updated: 06 January, 2015