Validation of the 18kDa Translocator Protein as a Novel Immunomodulator to Slow Progression in Parkinson's Disease

Study Rationale:
The immune system in the brain has two distinct modes: mode one is fighting infection and mode two is repairing injured nerve cells. In Parkinson's disease (PD), we think that the immune system goes into the wrong mode; instead of going into mode two, it goes into mode one. Fighting infection causes collateral damage so the immune system fails to protect nerve cells. We think that drugs which bind a protein called TSPO can be used to switch the behavior of the immune system out of mode one (fighting infection) into mode two (repairing nerve cells).

Hypothesis:
In pre-clinical models of PD, treatment with a drug that binds TSPO (XBD173) will switch the brain's immune system into repair mode and therefore protect nerve cells from death.

Study Design:
We will inject toxins into the brains of pre-clinical models to induce a disease state that resembles Parkinson's. Some of the models will be treated twice per day with XBD173 and others will receive placebo. Brains will then be analyzed to determine whether the drug can switch the behavior of the immune system and therefore reduce the severity of the disease.

Impact on Diagnosis/Treatment of Parkinson's Disease:
If XBD173 protects nerve cells in models and in people with Parkinson's, then it may have potential to slow neurodegeneration and, therefore, might be an important drug to treat people with Parkinson's.

Next Steps for Development:
The drug we are using (XBD173) is available for use in people. Therefore, if our results show that XBD173 can alter the behavior of the immune system and protect neurons, we can test whether it has the same effect in people with Parkinson's.