Professor Nadir Maraldi and his team at the Rizzoli Orthapaedic Institute in Bologna are investigating whether a type of skin cell, called melanocytes, could be used as a cellular model to study collagen VI-related myopathies. This research could provide a useful tool for testing potential treatments.
This project is supported by the Collagen VI Alliance, which is made up of Muscular Dystrophy UK, Cure CMD (USA), Muscular Dystrophy Ireland, AFM Telethon (France), Swiss Foundation for Research on Muscle Disease (FSRMM).
The researchers have carried out a number of experiments to find an efficient method to collect and grow the skin cells. They are now able to obtain stable, viable melanocytes within six to eight hours of a skin biopsy being collected, a process that previously took 24 hours.
They have also developed a method to quickly and easily assess mitochondria directly in a skin biopsy, rather than needing to extract the cells. Using this method, alongside a type of microscopy, the researchers have detected mitochondria with structural defects in the skin cells of people with Collagen VI-related myopathies.
These methods and observations indicate that melanocytes are a useful model to study faulty mitochondria in Collagen VI-related conditions.
What are the aims of this project?
In collagen VI-related myopathies there are changes to the structure and function of mitochondria (the parts of the cell that generate energy) in muscle cells. These changes trigger a biological pathway that leads to muscle cell death. To test potential therapies for their ability to correct the mitochondrial defects in collagen VI-related myopathies, muscle cells are collected via a muscle biopsy. However, this is an invasive procedure and the cells can be difficult to grow in the lab. Therefore better models are needed.
Professor Maraldi has recently shown that in people with collagen VI-related myopathies, some changes seen in the mitochondria of muscle cells are also seen in melanocytes (skin cells that produce pigment). In this project he will characterise these melanocytes further and assess whether they could be used as an alternative model to muscle cells.
Using the melanocyte cell models in a dish he will also test for potential new therapies. Drugs that inhibit the faulty mitochondria will be tested to see if they can stop the cell-death pathway.
Why is this research important?
Good models of a condition are needed to assess the effect of new treatments and to better understand the underlying biology that leads to muscle weakness.
This project will determine whether melanocytes are a good cellular model to test potential therapies for collagen VI-related myopathies. If so, clinicians could have a valuable tool to measure the effectiveness of potential therapies.
It is also important because melanocytes can be obtained from a skin biopsy, which is a less invasive procedure than a muscle biopsy.
How will the outcomes of this research benefit people with collagen VI-related conditions?
This research could provide a better cell model for testing effective inhibitors of the mitochondrial cell death pathway, which could aid the identification of a potential therapy. It would also reduce the need for muscle biopsies to test the new therapies.
How might this research impact on other neuromuscular conditions?
The faulty mitochondrial function that this project is investigating contributes to muscle cell death in other neuromuscular conditions. The development of therapies that inhibit faulty mitochondrial function might therefore benefit people with other muscle conditions.
Project leader: Professor Nadir Maraldi
Institute: Rizzoli Orthapaedic Institute, Bologna, Italy
Conditions: Ullrich congenital muscular dystrophy, Bethlem myopathy
Duration: One year, starting 2017
Total cost (£): 44,411
Official title: Melanocytes as low invasive tool alternative to muscle cells to assess mitochondrial therapies in collagen VI related myopathies
This research would not have been possible without individual donations, family fundraising activities, trusts and corporate support for our Ullrich CMD Appeal.
Donate now and help us ensure that effective treatments and expert care are available to all those living with collagen VI-related conditions, including Ullrich CMD. Thank you.