Understanding muscle weakness in VCP-associated multisystem proteinopathy type 1

DNA is like an instruction manual for the body. It tells cells how to make proteins, which help the body grow, move and stay healthy.

In a condition called VCP-associated multisystem proteinopathy type 1 (VCP MSP-1), there’s a change in the instructions for making a protein called VCP. This change means the VCP protein doesn’t work properly. VCP is a vital protein that helps manage many other proteins in the cell, acting like a quality control supervisor. Scientists are still learning how this faulty protein causes muscles to become weak.

Dr Rebecca Jones and her PhD student are trying to find out how changes in the VCP protein lead to muscle weakness in people with VCP MSP-1. The team is using cells grown in the lab to focus on three key areas that could help explain what’s going wrong in the muscles.

1. Muscle repair
Muscles get tiny injuries from everyday use. The body repairs them by making new muscle cells. For each new muscle cell, DNA needs to be copied and the VCP protein might help do that. By comparing cells with the faulty and working version of the protein, the team is checking if the faulty protein stops DNA from being copied correctly and if this gets in the way of the repair process.

2. Cell structure
Each muscle cell has a control centre (called the nucleus) with a protective layer around it. The team think the faulty VCP protein might weaken this layer, which could stop the cell from working properly. They’ll examine the molecules that make up this protective layer to see if they look or behave differently in cells with the faulty VCP protein.

3. Muscle fibre formation
Muscles are made up of long fibres, which are formed when many muscle cells join together. As this happens, the control centres (nuclei) move to specific places in the fibre. Correct positioning of these control centres is crucial for muscle strength. By growing muscle fibres in the lab, the team are investigating whether the faulty VCP protein causes the control centres to end up in the wrong place.

To find new treatments, scientists first need to understand what’s going wrong in the body. This research will help show how changes in the VCP protein affect muscles and cause them to become weak.

Only once scientists understand this better, can they start looking for ways to slow down or stop the condition.

Some of the muscle problems being studied in this project might also happen in other muscle wasting and weakening conditions. So, this research could help people with VCP MSP-1 and potentially lead to better understanding and treatments for other conditions in the future.