New Imaging Reveals Protein Flaw in Motor Neurone Disease

Scientists from the University of Sheffield's Institute of Translational Neuroscience (SITraN) have helped to identify pathological abnormalities associated with motor neurone disease using a new imaging technique.

The new technique, developed at the University of Birmingham, enables specific proteins to be examined 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.

The new method will help scientists better understand the changes in the brain that lead to motor neurone disease (MND) and could provide insights that will help with the development of new treatments.

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.

The SITraN scientists 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.

Dr Richard Mead from the Sheffield Institute for Translational Neuroscience, said: "We were very excited to apply this fantastic methodology which the team at Birmingham have developed to gain new insights into the biology of MND.

"We look forward to using the technology further to explore why motor neurons die and find new interventions for those affected by MND."

Professor Helen Cooper, lead researcher from the University of 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."

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.

The abnormalities were identified in a collaboration between the University of Birmingham and the University of Sheffield and published in the journal Nature Communications.