Longitudinal brain changes in childhood A-T

Dr Rob Dineen

Research Project information

Principal researcher: Dr Rob Dineen
Institute: University of Nottingham
Cost: £92,966 over 18 months in partnership with BrAshA-T
Start Date: April 2018

What are the researchers proposing to do?
Ataxia Telangiectasia (A-T) is a genetic condition that leads to nervous system problems, particularly loss of coordination of movement that progresses through childhood. In the previous study, called the CATNAP study, Dr Rob Dineen and team carried out brain MRI scans on 24 children with A-T and 24 without A-T. They found that measurements on the brain scan were markedly different between participants with and without A-T and some measurements showed a close relationship to the severity of the nervous system problems.

The team now plan to invite the CATNAP participants to return for another scan and assessment to show how the measurements have changed over 3 years compared to healthy children, and to see whether changes in MRI measurements match changes in the severity of the nervous system problems. They also hope to scan some very young children (3-6-years old) without sedation or anaesthetic.

This will give the researchers unique insights into how brain structure and function changes as children with A-T grow up.

By including very young children they hope to be able to demonstrate that with careful preparation by a play specialist using an MRI simulator, it is possible to successfully scan very young children and make the key measurements on the MRI scans in this age group.

How will the research be done?
The Nottingham team will invite children and young people who participated in the previous CATNAP study to re-attend for a further MRI scan and clinical assessment. There will be an average gap of 3 years (ranging from around 2 to 4 years) between the first and second visits for these participants, and this time interval will allow them to see how the MRI measurements have changed compared to healthy children, and how the changes in the MRI measurements reflect changes in the levels of disability.

They will invite very young children with A-T who are referred to the UK Paediatric A-T Clinic in Nottingham to take part in the study. These children will have the standard clinical assessment of their neurological disability. They will then undergo careful preparation by a play specialist using Nottingham’s new MRI simulator. Having an MRI can be challenging for young children, but they hope to make the experience a positive one for the children, allowing us to obtain the MRI measurements from this age group.

How could it make a difference to the lives of those affected by A-T?
This study will not in itself directly lead to benefit for people with A-T in the short term. Rather, this study and its predecessor (CATNAP) are important steps to establishing MRI measurements that tell us how brain tissue changes in A-T relate to nervous system disability. This improved understanding could be very helpful for developing new treatments to prevent or slow the progression of A-T, and for allowing Clinicians to measure the effects of new treatments in future clinical trials.

This study also hopes to prove that it is possible to perform MRI scans in very young children without sedation or anaesthetic. This will open the door to studying brain changes in children who are at the very earliest stages of A-T, i.e. those who stand to make the greatest lifelong gain from newly developed treatments.

MRI is already widely used in clinical practice, and most of the sequences used in this study are available on (or easily added to) modern clinical MRI scanners. Therefore, the brain MRI measurements could be easily used in clinical trials, and ultimately clinical practice, in any medical centre globally with modern day MRI facilities.