The aim of the UK DRI at King’s is to understand the very earliest molecular and pathophysiological events that initiate neurodegeneration and develop novel therapeutic strategies. Focusing on amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), researchers at the Centre aim to study the role of genes and molecular pathways involved in neurodegeneration.
Groundbreaking work at the Centre has revealed a key role for RNA-binding proteins in the onset and progression of ALS and FTD, which commonly mislocalise into cytoplasm and aggregate in affected cells. It remains to be determined how these defects deregulate cellular RNAs, and how such deregulation is linked to altered energy metabolism and other pathways implicated in these diseases through genetic risk variants or environmental responses. The teams aim to answer key questions such as:
- Which cell types are vulnerable to the genetic risk variants and environment-driven regulatory changes that drive ALS/FTD?
- How do the pathogenic mutations affect RNA processing, transport, translation?
- How does altered RNA binding and liquid-liquid phase separation affect the aggregation of key proteins?
- What role does dysfunction of the nucleo-cytoplasmic transport play in protein mislocalisation?
- How is disrupted RNA local translation linked to energy metabolism in the context of disease phenotypes?
The UK DRI at King’s has a clear translational trajectory, as researchers are designing, manufacturing, patenting, and testing RNA- and gene therapy-based potential therapeutics in preclinical models. In 2019, a spinout, AviadoBio, was launched from the Centre, co-led by Prof Chris Shaw, to develop innovative gene therapies to treat ALS and FTD.