Investigating the effects of commonly prescribed drugs on the prevention and treatment of Alzheimer's and other neurodegenerative diseases: are there drugs already available that can be repurposed?

Date of ISAC Approval: 
Lay Summary: 
Alzheimer's disease is a progressive disease affecting brain function and independent living, and eventually requires full-time care. There are only a few treatments that temporarily help symptoms such as memory loss; however, these eventually become ineffective as the underlying disease progresses unabated. Part of the difficulty of treating Alzheimer's disease is that it involves the activation of many destructive processes in the brain, each of which needs treatment simultaneously if the progression of the disease is to be halted. We hope to investigate the possibility of using a more time- and cost-effective method to reposition new drugs for the prevention or treatment of the disease. Drug development can take over 20 years and cost up to £1billion per eventually licensed drug. We wish to investigate the potential of using a number of existing drugs, already prescribed for other conditions that may offer protection to the brain, as a cheaper and more rapid method of identifying new drugs. To explore this we will test whether these treatments protect against or increase the risk of other neurodegenerative diseases, and to what extent this effect is further enhanced when existing dementia therapies are co-administered. This could then help to prioritise groups of drugs that may be beneficial in the treatment of a number of neurological conditions and therefore accelerate the formal testing of recognised safe and cost-effective drugs as new potential approaches for preventing or treating Alzheimer's and other neurodegenerative diseases.
Technical Summary: 
There is urgent need for new evidence about medications that could influence the incidence and progression of neurodegenerative diseases. One promising approach is to investigate drug repositioning, which offers a time- and cost-effective alternative to traditional drug development. A recent consensus study of dementia experts identified a short-list of individual and classes of prescribed drugs that may be repurposed as novel treatments for dementia. The short-list included compounds used to treat hypertension, hypercholesterolemia and type 2 diabetes, all of which could be classed as having 'cerebroprotective' properties and have variable levels of pre-clinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology. However as yet there is limited pharmacoepidemiological data to support their effects in human populations. Our primary aim, therefore, is to investigate whether these existing medications, previously identified as potentially cerebroprotective, could be repurposed to prevent or treat Alzheime''s disease and other types of dementia, amyotrophic lateral sclerosis and Parkinson's disease. We will conduct an observational cohort study to investigate the relationship of these medications with incidence and post-diagnosis survival of patients and at the same time identify to what extent any observed associations are altered when existing dementia therapies are co-administered. Collectively these findings will allow the prioritisation of drugs to be tested as repurposed treatments in clinical trials of these conditions in the future.
Health Outcomes to be Measured: 
Diagnosis of neurodegenerative disease of interest Death

Dr Patrick Kehoe - Chief Investigator - University of Bristol
Mr Luke McGuinness - Collaborator - University of Bristol
Dr Neil Davies - Collaborator - University of Bristol
Professor Richard Martin - Collaborator - University of Bristol
Venexia Walker - Collaborator - University of Bristol

HES Admitted;HES Outpatient;ONS;Patient IMD;Practice IMD (Standard)