Finding a therapeutic target for Cerebral Amyloid Angiopathy

Professor Geoffrey Cloud

by Loretta Piccenna, PhD
Research Manager, Department of Neuroscience, Central Clinical School

 An opinion piece published in the journal Stroke proposes the re-purposing of a potent existing drug, tranexamic acid (TXA), for the treatment of cerebral amyloid angiopathy (CAA), a devastating cause of stroke due to intracerebral haemorrhage and dementia.  

Professor Geoffrey Cloud, Director of Stroke Services, Alfred Health and Group leader, Department of Neuroscience at the Central Clinical School, said, 

‘Cerebral amyloid angiopathy (CAA) is a neurological condition that is increasingly being diagnosed in clinical practice, but sadly there is no specific treatment for patients.’ 

Diagnosis is based on the modified Boston criteria (specific criteria for CAA), MRI and / or CT scan. The increase in diagnosis may be due in part to the increasing longevity of the population we now see and the pattern of prevalence that increases with age and in people with dementia. 

In collaboration with Professor Robert Medcalf from the Australian Centre of Blood Diseases (ACBD), CCS and international partners in the UK (Professors David Werring, Stroke Research Centre, Queen Square Institute of Neurology, London, and Hugh Markus, University of Cambridge), the team have reviewed existing evidence on the pathophysiology and treatment for CAA. A couple of early phase clinical trials have not shown any effectiveness in preventing intracerebral haemorrhage in the disease, and no randomised clinical trials of secondary stroke prevention in the disease have taken place.

Increased amyloid deposition in the vessel walls of the brain is characteristic of CAA, but the cause is still unknown. Based on their review, the team proposes a novel potential mechanism for CCA-related intracerebral haemorrhage involving the fibrinolytic (clot-busting) system and using TXA. To test their hypothesis, randomised clinical trials are needed, which the team is pursuing now. TXA is an antifibrinolytic drug that is considered reasonably safe to use and is readily available. However, its safety for treatment and effectiveness in patients diagnosed with CAA are not known. 

At present the team are looking for financial support to enable successful completion of the clinical trial. If you are interested, please contact Ms Carrie Keller (Deputy Director, Development), +61 3 9903 4252 or by email, carrie.keller@monash.edu.

Reference 

Mutimer C, Keragala C, Markus H, Werring D, Cloud G, Medcalf R. Cerebral Amyloid Angiopathy and the Fibrinolytic System. Stoke. 2021; Published online 15 June, https://doi.org/10.1161/STROKEAHA.120.033107