Characterising pre-clinical models and testing gene therapy for X-linked spinal muscular atrophy

Professor Thomas Gillingwater and colleagues previously developed gene therapy to treat X-linked spinal muscular atrophy (XL-SMA); however, they were unable to test this due to a lack of animal models. In this project, the researchers will characterise a newly generated mouse model, which is much needed to test new treatments for XL-SMA.
Professor Thomas Gillingwater and colleagues previously developed gene therapy to treat X-linked spinal muscular atrophy (XL-SMA); however, they were unable to test this due to a lack of animal models. In this project, the researchers will characterise a newly generated mouse model, which is much needed to test new treatments for XL-SMA.

Project background 

XL-SMA is a type of SMA that causes progressive muscle weakness, mainly in boys. It is caused by changes in the UBA1 gene. Characterised by a lack of reflexes (areflexia) and the presence of contractures, not much is known about this form of SMA, and no animal models are available for it. This makes research into new treatments more challenging.  

Professor Gillingwater and his research team previously identified the potential of targeting UBA1 for therapies for all genetic forms of SMA. They have developed UBA1-targeted therapies but have been unable to test them due to the lack of animal models. Working with the Medical Research Council’s Genome Editing Mice for Medicine programme, Professor Gillingwater and his team have now developed a mouse model for XL-SMA, which will be characterised and used in this study. 

Project aims 

This project aims to understand the symptoms and features of the recently developed XL-SMA mouse model developed by Professor Gillingwater and colleagues. It’s important to know how mice with XL-SMA behave and how strong their muscles are, compared to mice without this condition. Once done, UBA1-targeted therapy will be tested on this model to investigate if the therapy is a viable treatment for XL-SMA. 

Why this research is important 

Little is known about the biology of XL-SMA. This has partly been due to the lack of animal models. This research will lead to a full characterisation of the first animal model of this condition, which will then be used for testing the first potential therapy for XL-SMA.