Study Rationale: Levodopa (L-dopa) is the primary medication used to treat Parkinson’s disease (PD). For L-dopa to exert its effect, it must enter the brain and be converted to the chemical dopamine. If this conversion occurs outside the brain, the efficacy of treatment will be diminished because dopamine cannot cross the blood-brain barrier. Recently, certain bacteria that reside in the gut were found to metabolize L-dopa to dopamine; this activity reduces the amount of L-dopa available to enter the brain and can consequently reduce the effectiveness of treatment.
Hypothesis: In this study, we will use viruses that specifically target bacteria to assess whether eliminating L-dopa metabolizing gut bacteria increases the drug’s bioavailability, potentially enhancing its effectiveness as a PD treatment.
Study Design: Using a system for growing bacteria, we will cultivate the L-dopa metabolizing species Enterococcus faecalis. We will then expose these microbes with a bacteria-specific virus (called a bacteriophage) and determine whether this infection eliminates Enterococcus faecalis and reduces the metabolism of L-dopa to dopamine. We will also produce a mouse model whose gut is colonized entirely by Enterococcus faecalis. Using these mice, we will determine whether targeting Enterococcus faecalis with bacteriophages limits L-dopa metabolism and enhances the bioavailability of the drug in mouse serum.
Impact on Diagnosis/Treatment of Parkinson’s disease: Only 5 to10% of the L-dopa taken by people with PD reaches the brain; the rest is metabolized in the gut and other peripheral tissues. We will determine whether targeting Enterococcus faecalis with bacteriophages will reduce this peripheral L-dopa metabolism and thereby increase the amount of L-dopa available to enter the brain.
Next Steps for Development: If this study is successful, we will next determine the effects that our bacteriophages might have on other gut bacteria. Furthermore, we will investigate whether these viruses can trigger any systemic or local immune responses that could limit its usefulness as a treatment.