Evaluation of a Drug that Removes Excess Iron from the Brain as a Treatment for Parkinson’s Disease

Study Rationale:
In Parkinson’s disease (PD), the death of cells in brain regions that control movement causes motor symptoms. Brain imaging studies show that iron builds up in these areas, damaging proteins and causing them to fold improperly. This misfolding causes proteins to form aggregates that impair and kill brain cells. PBT434 is a drug candidate that, when taken orally, enters the brain and removes excess iron. In pre-clinical models of PD, this treatment improves motor symptoms. Reducing excess free iron in the brains of people with PD may therefore slow disease progression. In this study, we will characterize the efficacy of PBT434 in pre-clinical models with brains more closely related to our own.  

Hypothesis:
PBT434 could reduce neuronal damage and improve motor function in pre-clinical models with experimentally induced PD. Studying these models will help us determine the optimal dosage for a clinical trial in humans.  

Study Design:
We will infuse a toxin that targets PD-related neurons into the brains of pre-clinical models, leading to neuronal death and PD-like motor symptoms. These models will then be treated for three months with a low dose of PBT434, a high dose of PBT434, or a placebo. We will monitor improvements in the models’ motor function and changes in their brain iron levels. At the end of the study, we will measure their blood levels of PBT434 and assess whether treatment boosted the survival of neurons and reduced the amount of free iron in the brain.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
The study will allow us to determine whether reducing brain iron will protect neurons and alleviate Parkinson’s motor symptoms in pre-clinical models. Measuring blood levels of PBT434 at the end of the study will help us to optimize dosages for human trials. We will also assess whether measuring the changes in free iron during treatment will provide a useful way to monitor disease progression.

Next Steps for Development:
The results of this study will be used to select the doses of PBT434 that will be used in the first Parkinson’s clinical trial.