A novel approach to reduce the
impact of progressive multiple sclerosis
In 2016, Dr Steven Petratos, Monash University Victoria was awarded a two year Project Grant by MS Research Australia, fully funded by the Trish MS Research Foundation.
Dr Petratos is the only Australian researcher to receive funding from the International Progressive MS Alliance in their inaugural round of funding. This Project Grant is a continuation of this research.
The International Progressive MS Alliance is working together to connect resources and experts around the world to find answers and develop solutions to end progressive MS. MS Research Australia, with whom the Foundation works closely, has joined MS organisations from around the world in a global alliance to end progressive MS. Coordinated by the MSIF, this Alliance is the most ambitious collaborative project the global MS movement has ever embarked upon.
The progressive phase of MS is thought to result from ongoing damage to the nerve fibres which may continue to occur in the absence of a 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’ group have identified a number of molecules which are involved in the destructive cascade in nerve fibres in the brain and spinal cord that follows inflammatory attacks. If they can stop this cascade from being triggered they could potentially prevent the progressive damage in MS. Dr Petratos’ team has been investigating a molecule known as NgR1 and attempting to block its activity in nerve cells. His team have shown the importance of this molecule in a laboratory model of MS. By preventing NgR1 from being made in brain cells of mice with and without a MS-like disease his team found that the absence of the molecule was associated with increased damage to the nerve cells of the brain. They also showed that they could replace NgR1 after it was removed, and this led to improved nerve cell survival in the face of the inflammatory attacks.
During the past year his group has optimised some technically challenging experiments in their laboratory model of MS. They will now enable them to move into a novel and exciting phase of the research, delivering NgR1 to the brain cells of mice with an MS-like disease using genetically modified blood stem cells. These cells will carry the molecule to the sites where it is needed in the brain. They will also test whether, once delivered, the molecule is making a difference in terms of the survival of nerve cells and if so what is the best timing to deliver the therapy. These experiments will help determine whether this is a potentially viable technique to develop a therapy to protect brain and spinal cord cells in people with MS.
By targeting these molecules during MS 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 additional funding from the Bethlehem Griffiths Research Foundation. The grant has also supported the work needed for several students in the laboratory to submit their PhD and honours theses, with a few more to be submitted at the end of 2017 or early 2018.