MS is a very varied disease and people experience different levels of disability. The majority of people with MS are diagnosed with a form of the disease called relapsing-remitting MS, which is characterised by acute attacks followed by periods of remission in which there is no disease activity or disability progression. Over a 15 to 20 year period, around half of these people will go on to develop a form of MS called secondary progressive MS where there is a gradual accumulation of disabilities. The rarest form, primary progressive MS, shows progressive disability from the start. Unfortunately, there are very limited treatment options for people with the progressive forms of disease.
The development of treatments for progressive MS is hampered by the current lack of understanding of the biochemical mechanisms that differentiate relapsing-remitting MS from the progressive forms. Associate Professor Crouch has discovered that copper which is normally found in the body, is not distributed normally in the body of people with progressive MS. He suggests this may affect the function of some of the body's enzymes, leading to changes in the biochemical processes in individual cells.
The aims of this project were to measure the distribution and amount of copper in tissue from the spinal cord in people with and without MS, understand how copper in the body influences the molecular mechanisms that underpin progressive MS, and to trial a potential copper delivery therapy in laboratory models of MS.
Associate Professor Crouch and his research team have generated promising data that helps reveal the role that copper might be playing in the development of progressive MS, and its potential as a therapeutic target. Their analysis of copper levels of tissue from people with MS also supports these findings and indicates that the laboratory findings may mirror the situation in humans.
Associate Professor Crouch and his team delved deeper into the mechanisms underpinning the connection between copper and MS. They determined the levels of copper in human spinal cord tissue affected by progressive MS and found that copper levels appeared to be lower than the amount required in the spinal cord. In hand with this, levels of genes involved in handling copper, and enzymes containing copper, were also altered.
Using a drug to deliver copper to the brain in two laboratory models of MS, the team found that the treatment improved activity of copper-containing enzymes, improved myelination of the nerve cells in the brain and spinal cord and protected nerves from further damage, resulting in better neurological function. These findings have been presented at national and international conferences and have attracted exciting international collaborations.
This work strengthens the team’s hypothesis of the role of copper in MS, and the potential for copper drugs to be considered as a new treatment option for progressive MS. The drug used in this study, CuII(atsm), is not specific to the brain and spinal cord, and could be toxic to tissues such as liver and kidneys that already have sufficient copper levels. Going forward, the team is working with synthetic chemist Professor Paul Donnelly to develop a new family of copper delivery drugs that are specific to the brain and spinal cord.
Updated: 31 March 2022
Updated: 05 January, 2018