Finding a treatment for Vascular Dementia

The Researchers
Professor Ashley Bush, Head, Neurodegeneration Oxidation Biology Unit, Florey Institute, Melbourne

Professor Bernard Lerer, Director, Biological Psychiatry Laboratory, Hadassah Medical Center, Jerusalem

Dr Amit Lotan, Psychiatrist, Hadassah Medical Center, Jerusalem

Background
Currently 25% of all Australians over 85 are suffering from some form of dementia and it is projected that by 2060, 50% of all people in Australia over 85 will develop some form of dementia. While Vascular dementia (VaD) currently accounts for around 20% of all dementia cases, it is increasingly being recognised as being present in other types of dementia as well, most notably being from Alzheimers disease.

Prof Bush, has shown that patients with dementia have excess iron in their brains which results in a process called ferroptosis (cell death caused by excess iron). He has developed a specialised assay for assessing the levels of iron in the brains of mice with vascular dementia. Professor Lerer has developed a bilateral common carotid artery stenosis (BCAS) mouse model for observing vascular dementia.

Study aim
The aim of the research is to develop a novel therapeutic approach for preventing or delaying the onset of vascular dementia. The approach involves using an iron chelator which has the specific effect inhibiting ferroptosis by binding excess iron and removing it from the brain. This research lays the groundwork for future studies in patients.

The research

The first stage of the project involved validation of the BCAS model. The results showed that the structural damage in white matter and its accompanying cognitive deficits were correlated with MRI data. This research has been submitted for publication and AUSiMED’s support is acknowledged.
Further experiments were performed to:
- a) validate preliminary evidence that increased iron deposition in the brain may be a key factor in the development of vascular dementia; and
- b) assess the effectiveness of ferroptosis inhibitors in delaying vascular dementia.

Preliminary findings indicate a unique effect for a ferroptosis inhibitors on depressive phenotypes related to vascular dementia/depression.