Preclinical validation of an orally active Nurr1 activator for neuroprotection and disease modification in Parkinson’s disease



Nurr1 was initially discovered as an orphan nuclear receptor involved in the differentiation and survival of midbrain DA neurons during brain development. Recent studies, however, have shown that Nurr1 plays an important role also in the adult brain, and there is evidence from studies in PD patients that impaired Nurr1 function is implicated in the pathogenesis of PD.
Thus, Nurr1, and its target genes, as observed in both rodent models and in human PD, are down-regulated in midbrain DA neurons expressing increased levels of the disease-causing protein α-synuclein. This includes a marked reduction in the expression of the GDNF receptor Ret, which in turn results in an almost complete blockade of GDNF signaling in the affected neurons.
Clinical and experimental data suggest that impaired Nurr1 function plays an important role in the cellular defense against α-synuclein toxicity, as well as in the appearance of DA neuron dysfunction, as seen in early stages of the disease, pointing to Nurr1 as an interesting target for therapeutic intervention. The goal of this project is to validate, in a series of pre-clinical tests, the potential of a novel, orally active Nurr1 activating drug, IVA3132, for neuroprotective and disease modifying therapy in early stages of PD.
Gällande start-/slutdatum2015/12/012017/11/30


  • The Cure Parkinson´s Trust

Ämnesklassifikation (UKÄ)

  • Medicin och hälsovetenskap