Development of Nurr1-RXR Heterodimer Selective Agonists for Parkinson's Disease

Promising Outcomes of Original Grant:
We hypothesized that Nurr1 could be targeted indirectly with small molecules through other nuclear hormone receptors, and that such compounds would have neuroprotective effects in models of Parkinson’s disease (PD).  We succeeded in identifying Nurr1-RXR biased agonists and found that they were effective in restoring motoric function and neuronal health and survival in pre-clinical models lesioned with the neurotoxin 6OHDA.  We concluded that this strategy was an effective way to target Nurr1 and could potentially lead to disease modifying therapies for Parkinson’s disease.

Objectives for Supplemental Investigation:           
Future studies will focus on more fully characterizing the effects of Nurr1-RXR agonists to gain a clearer understanding of their therapeutic potential.  Other studies will focus on their pharmacokinetics to determine which dosing regimens could be most effective means of treatment. 

Importance of This Research for the Development of a New PD Therapy:       
If these studies are successful, they could potentially result in therapies that could halt the progression of PD and that would be substantially simpler and easier to administer to patients than the disease modifying therapies currently undergoing clinical trials.