Research focus
In the Karlström lab we focus on CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), the most common familial form of small vessel disease. The condition leads to a series of increasingly severe strokes and dementia. CADASIL is linked to the Notch3 protein which is an important signaling protein allowing cells to communicate with one another. Mutations in the NOTCH3 gene result in misfolded Notch3 accumulating around small and middle-sized arteries throughout the body. At present how these Notch3 deposits affect the surrounding tissues is unclear. The disease mechanisms may be further complicated due to altered Notch3 signalling. A number of genetic disorders such as familial Alzheimer’s disease are directly linked to protein misfolding, which strongly suggest that abnormal protein accumulation and deposits play a direct cytotoxic rile in the disease.
We aim to better understand the molecular mechanisms of this condition in order to develop therapeutics to tackle CADASIL. We hypothesise that if we can harness the immune system to clear the Notch3 deposits we can halt or potentially reverse CADASIL progression.
A successful treatment for CADASIL would provide a much-needed cure for many individuals and would pave the way for new small vessel disease therapeutics. Our inter-disciplinary project team has clinical and preclinical expertise in CADASIL, and vaccine development and drug discovery competence.