Lead Investigator: Dr Atticus Hainsworth
Institution: St George's, University of London
Grant type: Drug Discovery project grant
Duration: 24 months
Amount: $515,893 (this project amount is in dollars as it was awarded as part of a joint funding call with the Alzheimer's Drug Discovery Foundation - Alzheimer's Society is funding half of this amount)
Scientific Title: Repurposing the PDE5 inhibitor tadalafil for vascular cognitive impairment. A test of concept in older people
What do we already know?
Vascular dementia is the second most-prevalent cause of dementia, after Alzheimer's disease. Increasingly, it is clear that changes to blood vessels within the brain interact with Alzheimer's disease, to worsen the disease and speed cognitive decline.
The main cause of vascular dementia in older people is cerebral small vessel disease – disease in the tiny blood vessels that supply brain cells with oxygen and nutrients. Small vessel disease makes artery walls become thick and stiff, which prevents them from responding to the brain's changing needs for blood.
The result is damage to deep parts of the brain due to insufficient blood supply. Although small vessel disease can develop and progress over many years, giving many opportunities for treatments to intervene and help, there is currently no therapy for small vessel disease.
Drugs that stop an enzyme called PDE5 from working cause dilation of blood vessels. The best known of drugs that work in this way is sildenafil (sold as Viagra) used to treat erectile dysfunction. In this study the researchers will investigate whether tadalafil (currently marketed as Cialis) causes dilation of blood vessels in the brain, allowing a better blood supply to the brain areas susceptible to small vessel disease and vascular dementia.
What does this project involve?
These drugs are safe and well-tolerated, and it is well-understood how they work within cells. This study will be a 'test-of-concept' study, to confirm whether this is a sensible approach for use in human brain blood vessels. This stage is needed prior to progression to full-scale clinical trials.
This study will test whether the drug tadalafil increases blood flow to deep brain regions that are often affected by small vessel disease, vascular cognitive impairment and vascular dementia.
The drug will be given to 50 participants over the age of 65 who have small vessel disease exhibited through vascular problems or mild cognitive impairment – the participants will not have dementia however, as the ultimate aim is to test this drug as a preventative treatment rather than to treat people with vascular dementia.
How will this benefit people with dementia?
There are currently no treatments for vascular dementia, and no ways to prevent progression of symptoms to dementia in people with small vessel disease. However, it can take up to 20 years to develop a drug from scratch.
Our Drug Discovery programme takes drugs that already exist for the treatment of other conditions and develops them further as potential treatments for dementia.
If the results of this initial study are positive, it may be possible to take this drug into full-scale clinical trials and so progress this towards a treatment for the prevention of vascular dementia.
Can I take part in this trial?
The researchers are looking for people over the age of 50 who have had a small stroke or transient ischaemic attack over six months ago. The trial is taking place at St George's University Hospital, South West London.
Find out more about who can take part in this trial and how to contact the researchers.