MLR-1017 is a psychostimulant drug used clinically for a variety of neuropsychiatric and other applications, but has never been tested in Parkinson’s disease (PD). Levodopa is a commonly used drug to treat PD. However, long-term use induces complications such as movement disorders, sleep disturbances (nightmares, nocturnal confusion), and psychosis. We propose that MLR-1017, in combination with levodopa, would reduce the amount of levodopa required for treatment, thereby also reducing side effects such as movement and sleep disorders.
Pre-clinical models of PD, as well as other Symptoms & Side Effects models, will be used to test the hypothesis that MLR-1017 can reduce the amount of levodopa needed by PD patients to control their PD symptoms and related side effects. Because PD is a multi-symptom disease with deficits in motor, sleep, cognitive, and other systems, we propose to establish a “platform” of models to test the effectiveness of MLR-1017. We will compare the effectiveness of MLR-1017 with and without levodopa against untreated models in normalizing sleep/wake activity, cognitive and motor function, gastrointestinal function, and in improving responsiveness in a model of depression.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
It is proposed that MLR-1017 administered in combination with levodopa may improve PD treatment in multiple ways. During the day, MLR-1017 administration would promote wakefulness and minimize nighttime sleep disturbances. MLR-1017 use may also normalize brain dopamine levels following levodopa administration, allowing lower levodopa doses to be used. MLR-1017 may thereby reduce side-effects of levodopa treatment such as movement disorders and psychological dysfunction. Finally, sydnocarb may be neuroprotective, thus slowing the progression of PD.
Parkinson’s is a devastating disease waiting for more effective drugs to halt its progression and improve its symptoms. This project will determine if a potent drug used in other neurological disorders will also be useful in PD. Another important aspect of this proposal is the establishment of an efficient and comprehensive pre-clinical evaluation system, including relevant pre-clinical models and imaging endpoints, which can be used to identify additional drugs for treatment of PD.
The drug MLR-1017 was tested for it’s therapeutic benefit in pre-clinical models of Parkinson’s disease. MLR-1017 showed both behavioral and biochemical benefit in multiple experiments that modeled Parkinson’s-like symptoms. These studies also provided a new pre-clinical testing platform for screening other drugs to treat various symptoms of Parkinson’s, including sleep disturbances, gastrointestinal abnormalities, depression, and anxiety. Based on the positive results from this project, MLR-1017 will be further developed along a clinical path toward providing a new therapeutic treatment for Parkinson’s patients.