Investigating Connectivity and Neuroinflammation within Corticomotor Networks in Ataxia Telangiectasia: Improving our Understanding of the Clinical Phenotype

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Stephen Rose

Research Project Information

Principal Researchers: Professor Stephen Rose
Institute: Royal Children’s Hospital, University of Queensland, Australia
Project Completion Date: July 2013

 Project Overview

 Ataxia Telangiectasia (A-T) is caused by faults in a gene called ATM (Ataxia Telangiectasia Mutated). A range of symptoms are observed, including the loss of muscle coordination (ataxia) due to the damage of nerve cells (neurodegeneration) within the brain. Unfortunately, no current therapy can prevent progressive neurodegeneration and ataxia. However, structural studies of A-T patient’s brains provide exciting opportunities for identifying the connection between neurodegeneration and ataxia. Professor Stephen Rose’s research team aimed to study degeneration within the brains of A-T patients using two imaging strategies called diffusion magnetic resonance imaging (dMRI) and positron emission tomography (PET).

 Project Outcome

 Professor Stephen Rose’s research team identified defective brain structure and functioning in A-T patients using structural and dMRI imaging. Crucially, they developed a novel dMRI method for studying the white matter microstructures (a type of brain tissue) of motor pathways important for coordinated movements. Using this method, dMRI images were obtained for A-T patients and similarly aged healthy participants. Significantly, degeneration of motor pathways responsible for coordinated movements was observed for all the A-T patients analyzed.

The PET study has been suspended at this stage. This is due to the challenge of acquiring PET images in young A-T patients at high risk of radiation induced injury.

 Publications

 Sahama, I.; Sinclair, K.; Pannek, K.; Lavin, M.; Rose, S.; Radiological imaging in ataxia telangiectasia: a review. Cerebellum, 2014, 13, 521-530.

  • Sahama, I.; Sinclair, K.; Fiori, S.; Pannek, K.; Lavin, M.; Rose, S.; Altered corticomotorcerebellar integrity in young ataxia telangiectasia patients. Mov Disord, 2014, 29, 1289-1298.
  • Sahama, I., Sinclair, K., Fiori, S., Docke, J., Pannek, K., Reid L., Lavin, M., Rose, S. Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study. Neuroimage Clin, 2015, 9, 206-15.

 What Next?

The novel dMRI imaging strategy developed enabled the identification of damage to motor pathways responsible for coordinated movements in A-T patient’s brains. This technique therefore provides exciting opportunities for monitoring the progression of A-T and effectiveness of new treatments. In addition to this new method, the research group is currently developing a novel MRI imaging strategy for assessing lung function. Furthermore, the research group plans to evaluate new more sensitive PET imaging technologies on older A-T patients. These methods could further improve the clinical management of A-T patients.