ProfessorKay Double

I work at the interface between neuropathological (human tissue) research and quantitative neurochemistry, applying these skills to neurodegenerative disorders. I have a special interest in degenerative disorders that involve dysregulation of biometals, such as copper and iron, including Parkinson’s disease, the motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), and rare genetic disorders of metal dyshomeostasis, such Menkes disease and Wilson’s disease.  The aim of my work is to understand disease causes and mechanisms and to use this knowledge to identify potential new treatments that may have the potential to slow or halt these disorders. I am also investigating biomarkers that will enables these disorders to be diagnosed earlier and more accurately than currently possible.  

In my early career I demonstrated that neuromelanin, a uniquely human metal-binding pigment, plays an active neuroprotective role in the brain. This changed the dogma that neuromelanin pigment has a negative impact upon the healthy brain. I then showed that neuromelanin, and its interaction with biometals, is altered in the Parkinson’s disease brain and that these changes reflect the pattern of brain cell death in Parkinson’s disease.  This provided further evidence that changes in metal-associated pathways, and related mechanisms such as oxidative stress, likely contribute to cell death in Parkinson’s disease brain. This prompted me to investigate other metal-binding molecules and led to the discovery of entirely new type of proteinopathy associated with neuronal death in Parkinson’s disease brain. This proteinopathy is based upon the antioxidant protein superoxide dismutase 1 (SOD1) and we demonstrated similarities between this pathology in Parkinson’s disease, and previously described SOD1 proteinopathy that underlies nerve cell death in ALS.  Excitingly we showed this proteinopathy can be ameliorated by drug treatment, resulting in improved cell survival.  We are currently investigating a promising new treatment approach for Parkinson’s disease and ALS repurposing drugs known to modify the structure of this protein.  We are also developing technologies that can quantify, for the first time, levels of these important biometals in the nervous system of a living person. These technologies represent new tools that will enable clinicians to better diagnose metal-associated disorders and monitor drug treatment for improved efficacy and safety.