Measuring cerebral protein synthesis rates in Alzheimer's disease
Research type
Research Study
Full title
Measurement of cerebral protein synthesis rates in Alzheimer's disease using 11C-leucine PET: new mechanistic insights and a new goal for therapy
IRAS ID
181915
Contact name
Giovanna Mallucci
Contact email
Duration of Study in the UK
2 years, 0 months, 30 days
Research summary
A major problem facing doctors and scientists has been that our limited understanding of the processes that cause the death of brain cells in Alzheimer's and related "neurodegenerative" diseases means that no effective treatments exist. Giovanna Mallucci's laboratory has made major inroads into these mechanisms in the last three years. We have discovered a fundamental process, “the UPR”, that causes brain cell death in neurodegenerative diseases, by reducing cerebral protein synthesis rates. When we blocked this process with a drug-like compound in mice with neurodegenerative disease, memory was restored and brain cell death and clinical disease were prevented. In humans, post-mortem studies on the brains of patients with Alzheimer's and related diseases show that this same UPR pathway is also activated.
Our question now is whether the UPR over-activation that is active in mice with neurodegeneration also contributes to brain cell death in the brains of Alzheimer's patients, through reduction of protein synthesis rates.
The aim of this proposal is to see if we can detect this process in patients with Alzheimer’s disease, using a validated technique called PET scanning to measure protein synthesis rates in brain. If we find that these are reduced in Alzheimer's disease (as in the mice), we will have confirmed this is an important pathway in dementia and we will pursue new treatments targeting the UPR to prevent brain cell death and restore memory. A negative result is equally important, giving essential information that will avoid fruitless pursuit of wrong targets for therapy.
Prof Mallucci has assembled a team of experts from the University of Cambridge for this study: Franklin Aigbirhio and Tim Fryer are experts in PET scanning in neurodegenerative disease, and John O’Brien is an old age psychiatrist specialized in clinical research in dementia.
REC name
Wales REC 6
REC reference
16/WA/0364
Date of REC Opinion
5 Dec 2016
REC opinion
Further Information Favourable Opinion