One of the big unanswered questions of A-T is this: why do cells in the cerebellum, and particularly those called Purkinje cells or Purkinje neurons, die off in people with A-T, when other brain cells don’t?
It would be very helpful if we could get hold of some of these cells to study. However, the brain is a complex and sensitive organ and we can’t just take out important cells. This project aims to solve this problem by growing Purkinje cells in the laboratory.
This can be done by taking cells from an individual – usually skin cells – and reprogramming these to become stem-cells. Stem cells are cells that can become different kinds of cells, unlike most cells in the body, which can only produce copies of themselves. This project then aims to persuade these stem cells, via a long and complicated process, to turn into Purkinje cells.
This is an extremely difficult process, involving cutting-edge technology. Purkinje cells are very large and in the brain they are supported by and networked to many other different cells. It was only carried out for the first time, using normal cells, a couple of years ago. It is likely to be even harder to do in cells from people with A-T, which are therefore lacking the ATM protein.
However, this project, entirely funded by the AT Society aims to do just that. They will take skin cells from people with A-T and use these to try and created Purkinje cells in the laboratory. This is sometimes called ‘in vitro’, literally ‘in glass’. If the project is successful in making Purkinje cells, this will open the doors to experiments to help understand why these cells die and to screening for drugs to prevent this. All in all this is a very exciting project with huge potential.
The team carrying out this project is led by Prof. Domenico Delia and Prof. Marco Foiani of the FIRC Institute of Molecular Oncology (IFOM) in Milan. IFOM is an international cancer centre that hosts 20 groups and 300 scientists, with further laboratories in Singapore and India.
Prof. Delia is a very experienced and well-known figure in the world of A-T research. He has worked on creating stem-cells from people with A-T for many years. In June 2018
Prof. Foiani is Professor of Molecular Biology at the University of Milan and, since 2009, has been Scientific Director of IFOM.