Neuroprotective or neurorestorative therapies for Parkinson's disease are still evolving. We have identified a novel conserved dopamine neurotrophic factor (CDNF) protein which might be beneficial for the treatment of PD. CDNF possesses a survival promoting activity for rodent embryonic midbrain dopaminergic neurons in culture and it prevents toxin-induced degeneration of dopaminergic neurons in the pre-clinical model of PD. CDNF, like its homologs, the mammalian mesencephalic astrocyte-derived neurotrophic factor (MANF) and the drosophila (fruit fly) MANF, belongs to a new evolutionarily conserved protein family.
In this non-clinical research project we will study the significance of CDNF as a dopamine neurotrophic factor, and analyze whether CDNF keeps alive or regenerates dopaminergic neurons that die in patients with Parkinson's disease. We will create CDNF-deficient mice and study whether CDNF is the survival and maintenance factor for mouse dopaminergic neurons. Using these mice and the pre-clinical model of PD we will study the effect of CDNF-treatment on motor symptoms in these animals.
We have also created drosophila DmMANF-deficient mutants which are used to study the mechanisms of DmMANF action. Using the drosophila genetics and biochemical methods we aim to identify the MANF and CDNF receptor.
Final Outcome
As a result of Dr. Saarma's work, CDNF was shown to be neuroprotective in animal models of PD. MJFF is working with Dr. Saarma to support his ongoing efforts to further characterize CDNF.