Scientists have discovered a molecule that could aid the development of new treatments for motor neurone disease, a new study suggests
Motor neurone disease (MND) is a life-shortening condition that causes muscle weakness, which typically worsens over a few months. There is no cure available, but treatment can help manage symptoms.
A team from the University of Edinburgh and the Max Planck Institute of Molecular Cell Biology and Genetics has identified a molecule called lipoamide. This molecule has the potential to revolutionise the treatment of motor neuron disease (MND) by preventing the formation of liquid droplet structures inside cells, which are linked to the progression of MND.
The findings are published in the journal Nature Chemical Biology.
New treatments are crucial for MND patients
With most people succumbing to MND within two years of diagnosis, and existing medicines unable to halt its progression, the need for new treatments is pressing and undeniable.
The researchers discovered lipoamide’s effects after an extensive screening process. They screened 1,600 molecules to identify those affecting the formation of liquid droplets – known as stress granules – in cells. This rigorous process led them to the discovery of lipoamide’s potential in treating MND.
The build-up of solid clumps of proteins inside stress granules, which typically form only briefly when cells are under stress, is one of the hallmarks of several neurodegenerative diseases, including MND.
Unclear why lipoamide has beneficial effects
They are promising targets for MND therapies as dozens of mutations in proteins bound up in the deposits are linked to disease-causing defects that arise in motor neurons, the researchers comment.
Previous research has suggested that mutations in two proteins, FUS and TDP-4, alter the formation and persistence of stress granules within cells. As a result, the proteins are prevented from fulfilling their key roles in repairing DNA and regulating cell function.
Lab tests in fly and worm disease models, as well as on motor neurones derived from MND patients, showed that lipoamide can dissolve existing stress granules and prevent new ones from forming. This is a significant finding as it suggests that lipoamide not only halts the progression of MND but also reverses some of its effects. Further analysis found that lipoamide also improved cell health, neuronal structure, and motor function.
“Identifying lipoamide powerfully demonstrates that drug-like molecules can target unstructured protein regions, with beneficial effects in experimental models of disease. Neurodegenerative diseases in people are often associated with unstructured proteins, making this an important demonstration of a potential new area for drug development,” commented Dr Richard Wheeler, School of Biological Sciences.
Lipoamide’s unique ability to target the floppy, unstructured parts of proteins required to form stress granules sets it apart from most drug molecules, making it a fascinating area of study.
The findings are positive, and researchers now have a new way of targeting MND-associated proteins. However, it remains unclear exactly why lipoamide has beneficial effects. More research is needed to understand whether this is an effective new way to combat the build-up of stress granules leading to MND, the researchers added.
