Study Rationale: In addition to the well-recognized movement abnormalities associated with Parkinson’s disease (PD), gastrointestinal symptoms such as constipation, leaky gut and inflammation are also common and can be troubling. There are few effective treatments for these symptoms in PD, in part because of a lack of suitable preclinical models that would enable testing of potential treatments. This project will develop animal models of PD’s gastrointestinal symptoms that are reliable, readily available and easy to work with. These preclinical models will then be used to test two novel mechanisms that hold promise for the treatment of the gastrointestinal symptoms of PD.
Hypothesis: This project will test whether drugs acting via two novel mechanisms have positive effects in animal models of the gastrointestinal symptoms associate with PD and thus have the potential to treat these symptoms in people with the condition.
Study Design: We will use multiple methods to induce, in mouse gastrointestinal tissues, the pathological changes that are thought to be responsible for the gastrointestinal symptoms in PD. The mice will then be tested for the presence of these pathological changes and for changes in gastrointestinal function that mimic the symptoms seen in people with PD. Drugs that act via two different novel mechanisms and that are retained in the gut with minimal absorption into the blood will then be tested for their ability to ameliorate the gastrointestinal pathology and symptoms.
Impact on Diagnosis/Treatment of Parkinson’s disease: There are currently no drugs approved for the treatment of the gastrointestinal symptoms of PD. If successful, this project will identify drugs that can potentially address this unmet need, reducing these very troublesome symptoms in people with PD.
Next Steps for Development: The drugs to be tested in this study are analogues of compounds that are already being tested in humans. If they demonstrate reduction of gastrointestinal symptoms of PD in this study, they could quickly be moved into clinical development.