The progressive phase of MS is thought to result from ongoing damage to the nerve fibre rather than the direct inflammatory attack on myelin. It is believed that destruction of the nerve fibres leads to permanent and increasing disability in progressive MS. Dr Petratos has been working on determining which molecules are responsible for this nerve fibre damage so that we can potentially stop it.
Using a laboratory model of MS, Dr Petratos’s group have identified a number of molecules that respond to the immune system damage, leading to a destructive cascade in the nerve fibres in the brain and spinal cord. If they can stop this cascade from being triggered they could potentially prevent the progressive damage in MS. In this project grant from MS Research Australia, fully supported by the Trish MS Research Foundation, Dr Petratos’ team will investigate a molecule known as NgR1 and attempt to block its activity in nerve cells. The blocking agent of NgRI will be delivered using a highly novel method that will allow accurate targeting of the NgR1 receptor.
Dr Petratos and his team are interested in specific molecules that are part of the molecular cascade that causes nerve fibre damage in MS. During this project, Dr Petratos demonstrated that one of the molecules, NgRI was key to nerve fibre damage and that damage was caused by NgRI interrupting molecular transport along the nerve fibres. By blocking NgRI, Dr Petratos showed that the transport of molecules along the nerve fibre was restored and that this reduced the amount of nerve fibre damage and symptoms seen in the MS-like illness in the mice.
The second part of this study involved the use of some highly novel and challenging techniques to allow the delivery of a therapeutic protein to sites of damage in a laboratory model of MS. This delivery system is based on immune cells in the blood and means that the therapeutic protein can work directly on the areas of damage. Dr Petratos and his team were able to demonstrate delivery of the therapy at the height of MS symptoms in a laboratory model of MS. Â Excitingly, the therapy was able to reduce the symptoms of the MS-like disease and the nerve fibres were able to regrow and myelin damage was repaired.
It is hoped that if a similar system could be used in humans, it may be possible to limit the destruction which occurs to nerve fibres in the brain and spinal cord, giving a better clinical outcome for people with MS.
This grant has enabled the group to obtain funding from the Bethlehem Griffiths Research Foundation, submit three PhD, one Masters and two honours theses developing the next generation of MS researchers.
Updated: 20 April 2018
Dr Steven Petratos
$160,000
2016
2 years
Past project