Objective/Rationale:
Patients with Parkinson’s disease (PD) have altered progression of ingested aliments/liquid from their stomach to the intestine, as well as suffer from constipation, and there is no efficient remedy to alleviate these digestive problems. The most commonly used drug to treat PD, levodopa, also makes the stomach empty more slowly. A new drug named anamorelin, which acts like a natural gut hormone ghrelin, makes the gut content to move faster. We plan to test whether pre-clinical models who have PD and are treated with levodopa, if anamorelin will improve the impaired gut propulsive motor function.
Project Description:
Experimental studies will be conducted in pre-clinical models with PD symptoms induced by chemical destruction of dopamine neurons in the brain and then treated or not with levodopa/carbidopa. We will assess the time taken by a viscous solution to be emptied from the stomach under those conditions with simultaneous anamorelin treatment. The drugs will be given to pre-clinical models orally. We will also test whether anamorelin improves the propulsive colon movement in pre-clinical models with PD, and in another experimental genetic model of PD in pre-clinical models. The technique to assess movements in the colon is based on monitoring changes in colonic pressure by a mini pressure sensor inserted into the colon, as well as defecation. The number and frequency of propulsive contractions are analyzed.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If anamorelin improves the transit of gut content in these experimental pre-clinical models with PD treated with levodopa, it will provide preclinical evidence to pursue clinical trial in patients with PD. These data may provide new treatment to ameliorate slow stomach transit and related levodopa uptake and relieve constipation. In addition, it may help to reduce the side effect of levodopa on the gut.
Anticipated Outcome:
It is expected that our studies with ghrelin agonists will provide the basis for new treatment to improve PD symptoms, related to the delayed stomach emptying and constipation. Since anamorelin is already in clinical trials for patients with low appetite and body weight loss, tt will be safe to use it in PD patients, not only to reduce the gut disorders but also weight loss that can be associated with PD.