Dr Ritwick Sawarkar, Group Leader at the MRC Toxicology Unit, alongside Dr Kadri Seppa, a Postdoctoral Researcher in the lab, have been awarded €150,000 from the European Research Council (ERC) to develop a novel mRNA therapeutic approach to treat Alzheimer's disease.
Dementia affected 55 million people in 2020, and cases are estimated to double every 20 years. Alzheimer's disease is the most common form of dementia globally accounting for 60-70% of cases. Yet, despite decades of research, progress towards more effective treatments, or even a cure, has remained modest.
Alzheimer’s disease is characterised by the accumulation of so-called amyloid plaques – a cluster of the misfolded protein beta-amyloid between neurons – which leads to neuronal stress, disrupted cell-to-cell communication and ultimately irreversible loss of those neurons. Interestingly, therapeutics aimed at clearing these plaques have seen limited clinical benefit, and many patients with significant amyloid plaques do not have memory loss. This suggests that there is more to this disease than the presence of these proteins alone.
As part of this ERC-funded project, the Sawarkar group will use their expertise on cellular stress pathways to develop and validate a mRNA therapeutic approach that restores the brain’s resilience to stress.
“Our lab recently discovered a novel stress resilience mechanism, which we named SITA (Stress-Induced Transcriptional Attenuation). It enables cells to turn off non-essential transcription during an event of cellular stress, such as protein misfolding, to spare resources to restore normal conditions within the cell. This project will test whether delivering enhancer proteins that reactivate this protective response to stress, that is lost in diseased brains, and reduce disease phenotypes in mouse models of Alzheimer's disease” shared Dr Kadri Seppa.
Dr Ritwick Sawarkar added “This first-in-class therapeutic looks at the root cause of neurodegeneration and how we may be able to rectify what has gone wrong. It would shift the way we think about treating neurodegeneration from removing protein build-ups to improving cellular resilience and pave the way for a novel, scalable and clinically relevant therapeutic avenue for Alzheimer’s disease using mRNA therapeutics.”
Sawarkar’s project is one of the proposals from across Europe that have been selected for funding as part of the EU’s research and innovation program Horizon Europe. These ERC proof of concept grants bridge the gap between pioneering research results and the early phases of commercialisation or society application.
Congratulations to the Sawarkar lab on receiving this prestigious award and for an exciting project. Read more about the ERC Proof of Concept Grants here.