Study Rationale:
Previous studies have shown that the body's immune response is involved in Parkinson's disease. This includes inflammation in the brain as well as systemic inflammation. One recent study has found that T lymphocytes, a type of white blood cell, recognize parts of the alpha-synuclein protein. This protein becomes abnormally aggregated in Parkinson's disease and is thought to cause some of the damage to the dopamine-producing brain cells affected in Parkinson's. Inflammation that may occur in response to these alpha-synuclein aggregates can damage brain cells further, so it is important to determine exactly how this happens and whether it can be targeted by existing drugs.
Hypothesis:
Our hypothesis is that an early immune response to alpha-synuclein aggregates is associated with worsening Parkinson's disease progression.
Study Design:
We are planning to measure antibodies to different forms of alpha-synuclein and to another protein that becomes aggregated in Parkinson's disease (i.e., tau) to see whether these are related to other measures of immune activation. We are using a cohort of patients based in Germany who have REM sleep behavior (RBD) disorder. Previous research suggests that a large proportion of these patients go on to develop Parkinson's disease, so they provide a window into early disease processes. We will compare them to healthy controls and to patients with established Parkinson's disease. In addition, we will be able to compare patients who have an abnormal DaTscan (suggesting early loss of dopamine-producing cells) with those who have a normal DaTscan (and are therefore less likely to progress to Parkinson's).
Impact on Diagnosis/Treatment of Parkinson's disease:
We hope that this will help us to understand part of the role of the immune response in early Parkinson's disease. While this is not likely to play a significant role in diagnosis, it could help stratify patients at risk of disease progression and identify those most likely to benefit from targeting inflammation.
Next Steps for Development:
If we are able to determine the processes involved in the immune response to alpha-synuclein, we could identify existing drugs approved for other conditions that could be repurposed to treat inflammation in Parkinson's. Such drugs could be used in clinical trials for Parkinson's relatively quickly with the goal of preventing disease progression in early stage patients.