Researchers co-funded by The SMA Trust and Muscular Dystrophy UK have discovered a new role for the SMN protein, which is reduced in people with spinal muscular atrophy (SMA). These findings improve our understanding of SMA and will help to develop future treatments.
What were the researchers aiming to do?
SMA is a condition which affects motor neurons (the nerves that connect the spinal cord to muscle), causing them to deteriorate and eventually die. The reasons for this are still unclear. Recent evidence links neurodegenerative diseases like SMA to defects in the production of new proteins inside cells. This process is called translation and relies on a piece of machinery inside the cell called the ribosome (see figure below).
With support from The SMA Trust and Muscular Dystrophy UK, Professor Tom Gillingwater and colleagues at the Universities of Edinburgh, University College London and Trento in Italy, investigated the role of the SMN protein in translation.
What did they find out?
Professor Gillingwater and his team found that the SMN protein regulates translation by influencing the ribosomes. Experiments in a mouse model of SMA showed that SMN deficiency leads to fewer ribosomes in the axons of the motor neurons.
Further experiments also demonstrated that defects in translation and ribosomes are important factors that contribute to the breakdown and loss of motor neurons in SMA. These defects can however be reversed using SMN-increasing therapies.
How might this help people living with SMA?
These findings improve our understanding of the underlying biology of SMA, which is key to developing effective treatments. This study has highlighted problems with the ribosome, which could potentially be targeted with a drug.
Professor Gillingwater said:
We are excited by these new research findings that have uncovered new insights into how motor neurons live and die in SMA. This significantly enhances our understanding of the workings of the neuromuscular system in health and disease, with potential implications for developing and testing new treatments for SMA and related conditions. This work would not have been possible without the generous support received from the SMA Trust and Muscular Dystrophy UK. We are therefore very grateful to them and their supporters.
The study was published in the scientific journal, Cell Reports.