Does Dopamine Cell Death Result from a Novel Proteinopathy

Project Summary

This project characterizes a highly novel, promising new target where compelling data supports our argument that wildtype SOD1 proteinopathy plays a key role in dopamine neuron death in Parkinson’s disease brain.  A positive outcome in this study will prove a role for SOD1 proteinopathy in Parkinson’s disease and thus reveal an innovative target for the development of disease-modifying treatments.

Principal Investigator

Associate Professor Kay Double

Study Rationale

We have recently shown that a new type of toxic protein forms in the brains of people with Parkinson’s disease.  This same protein is known to cause nerve cell death in another degenerative disorder which affects movement. We therefore suggest this abnormal protein may underlie the death of brain cells in Parkinson’s disease.         

Hypothesis

In this study we will use a mouse model which reproduces this abnormal protein in the brain to test whether the development of the toxic protein causes dopamine neurons to die.

Study Design

We will investigate how the abnormal protein forms in the mouse model, then validate these findings in human Parkinson’s disease brains. Finally we will use our mouse model to test if modification of this protein by a drug we recently developed will stop the formation of the toxic form of the protein and rescue dopamine brain cells from death.

Impact on Diagnosis/Treatment of Parkinson’s disease

This project may reveal why dopamine cells die in Parkinson’s disease and how these cells can be protected from the disease process.        

Next Steps for Development

If successful, we will then test our new drug in Parkinson’s disease patients. A positive outcome could result in a new treatment that, for the first time, slows or stops disease progression.