Imaging technique uncovers protein abnormality in motor neurone disease

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

The method will help scientists better understand the changes in the brain that lead to motor neurone disease (MND) and could eventually yield insights that will help with the development of new treatments. The abnormalities were identified in a collaboration between the University of Birmingham and the University of Sheffield and published today [8 Aug] in Nature Communications. 

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

At the University of Birmingham researchers have developed a technique that enables them to examine specific proteins in their native state, directly from brain and spinal cord tissue samples. Called native ambient mass spectrometry (NAMS), the tool enables the structure of proteins to be studied in relation to their location within the tissue in greater 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 been implicated in motor neurone disease previously but this is the first time that detailed molecular imaging has been able to show how versions of the protein with missing metal ions accumulate in the affected mice. 

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

Richard Mead from the Sheffield Institute for Translational Neuroscience said: “We were very excited to apply this fantastic methodology which Helen’s team have developed to gain new insights into the biology of MND and we look forward to using the technology further to explore why motor neurons die and find new interventions for those affected by MND.” 

The next steps for the researchers will be to test to see if the same imbalances are present in human tissue samples, and to try to treat the imbalance in the mice using available drug compounds.  

ENDS 

For media enquiries, interviews, or an embargoed copy of the research paper please contact Press Office, University of Birmingham, tel: +44 (0)121 414 2772 or email pressoffice@contacts.bham.ac.uk 

Notes to editor: 

• The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 8,000 international students from over 150 countries. 

• The University of Sheffield is a leading Russell Group university, with a world-class reputation. Over 30,000 students from 150 countries study at Sheffield. In a truly global community, they learn alongside over 1,500 of the world’s leading academics. 

• ‘Native ambient mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation, not monomerization, in the development of pathology’ – Oliver J. Hale, Tyler R. Wells, Richard J. Mead, and Helen J. Cooper is published in Nature Communications. 

• The Sheffield Institute for Translational Neuroscience (SITraN) has increased the visibility of neurological diseases research in the UK. The Queen’s Anniversary Award 2019 and The Future NHS Parliamentary award 2019 recognised the impact it has had in developing new treatments that give hope to patients and carers in the UK and worldwide. SITraN is an essential development in the fight against motor neurone disease and other common neurodegenerative disorders including Parkinson’s and dementia, as well as stroke and multiple sclerosis.