Pathological abnormalities associated with motor neurone disease have been identified using a new technique developed at the University of Birmingham.

This method will allow scientists to better understand the changes in the brain that lead to motor neurone disease (MND) and could provide insights to help develop new treatments. The abnormalities were identified as part of a collaboration between the University of Birmingham and the University of Sheffield and published today (8 August) in Nature Communications.

Motor neurone disease, also known as amyotrophic lateral sclerosis or ALS, is a disease that causes muscle wasting, caused by messages from the brain's motor neurons not reaching the muscles, causing them to weaken. Around 5,000 people in the UK have the condition at any one time and there is currently no cure.

Researchers at the University of Birmingham have developed a technique that allows them to examine specific proteins in their native state, directly from tissue samples from the brain and spinal cord. This tool, called native ambient mass spectrometry (NAMS), allows the structure of proteins to be studied based on their location in the tissue in more detail than ever before.

Working with colleagues at the University of Sheffield, they were able to identify a metal deficiency in a specific protein, known as SOD1, and show that it accumulates in specific regions of the brain and spinal cord in mice with MND.

SOD1 has previously been implicated in motor neuron disease, but this is the first time that detailed molecular imaging has been able to show how versions of the protein lacking metal ions accumulate in affected mice.

Helen Cooper, a senior researcher at Birmingham’s School of Biosciences, said: “This approach is the first to show that this form of SOD1 correlates with motor neurone disease pathology. This is a very early step towards discovering treatments for MND and is also an exciting new avenue for understanding the molecular basis of other diseases in unprecedented detail.”

We were very excited to apply this fantastic methodology that Helen's team developed to gain new insights into the biology of ALS and we look forward to continuing to use this technology to explore why motor neurons die and find new interventions for people affected by ALS.

Richard Mead of the Sheffield Institute of Translational Neuroscience

The researchers' next steps will be to test whether the same imbalances are present in human tissue samples and to try to treat the imbalance in mice using available pharmacological compounds.