Toward a cure for Parkinson’s disease: bench to bedside & bedside to bench
Based on our studies of transcriptional regulatory cascade underlying development and maintenance of midbrain dopaminergic (mDA) neurons, we identified the orphan nuclear receptor Nurr1 as a promising therapeutic target of PD. Although Nurr1 was viewed as a ligand-independent, constitutively active transcription factor, we identified both synthetic and endogenous ligands of Nurr1 that prominently regulate Nurr1’s function via direct interaction, suggesting that (1) Nurr1 is an “adopted” nuclear receptor (thus, “druggable”) and (2) Nurr1 is druggable and its agonists can be developed as a novel class of mechanism-based, disease-modifying therapeutics for PD. In addition, given that major motor dysfunction of PD is caused by selective degeneration of midbrain dopamine neurons, cell replacement is a promising approach for PD. Thus, we are developing and optimizing human iPSC-based transplantation for autologous, personalized cell therapy and recently treated the first PD patient using the patient’s own cells. At the same time, this clinical study revealed new challenges to be addressed. I will discuss how basic molecular studies can be translated into novel therapeutic approaches for PD and vice versa, demonstrating a proof-of-concept of “bench to bedside” and “bedside to bench” approaches.
~Coffee/tea will be served prior to the lecture~
Hosted by Professor KiBum Lee