Exploring how muscle damage spreads in VCP-associated multisystem proteinopathy type 1

VCP-associated multisystem proteinopathy type 1 (VCP MSP-1) is caused by changes in the VCP gene. Genes are like instruction manuals that tell cells how to work. One of their jobs is to help make proteins, which do important tasks in the body. The VCP protein helps clean up damaged or old proteins in cells.

When the VCP gene is changed, the protein doesn’t work properly. This can cause the build-up of other proteins in cells, known as clumps. These clumps can harm muscles, bones, and the nervous system.

Muscle weakness is a common symptom of VCP MSP-1, but it can affect people differently. Some people get worse quickly, while others have milder symptoms. Scientists are now trying to find out why this happens, how muscle weakness starts and changes over time, and how damage might spread between cells.

Professor Jordi Diaz-Manera is using muscle samples from people with VCP MSP-1 to learn what happens inside muscle cells as the condition starts and gets worse.

1) Understanding differences in gene activity
All our cells have the same genes, but not all genes are ‘switched on’ all the time. This can change over time, especially if cells are damaged. The team is studying which genes are switched on or off in healthy and damaged muscle cells. This could help them understand what happens to cells as the condition progresses.

2) The effect of different VCP gene changes
There are over 50 known changes in the VCP gene. Each one might affect muscles in a different way. Understanding these differences could explain why symptoms vary and how the condition develops.

The team will grow ‘mini muscles’ in the lab, which behave like real muscles from people with VCP MSP-1. They will study how different gene changes affect muscle structure and function. They’ll also look at how these changes affect other important cells, like motor neurons, which carry messages from the brain to the muscles.

3) How the condition might spread
In VCP MSP-1, small areas of damaged muscle cells appear next to healthy ones. This suggests damage might spread from cell to cell. One idea is that the protein clumps inside damaged cells might cause proteins in nearby cells to start clumping too, which can stop them from working properly. Another idea is that damaged cells might release harmful substances that affect the cells around them.

To test this, the team will grow mini muscles with and without the condition and connect them with fluid – like how muscle cells are linked in the body. They’ll study which molecules are released and how cells communicate, including whether nearby supporting cells also send signals that affect muscle health.

To find new treatments, scientists need to understand what’s going wrong in the body. This research could help explain why symptoms are different from person to person, and how the damage spreads. This knowledge could, eventually, lead to new ways to treat or slow down the condition.