GDNF vs Neurturin: Is one better than the other?

Both GDNF and neurturin (NTN) have been in Phase II clinical trials for PD and NTN is currently being tested in a Phase I/II trial. Both are members of the GDNF family of ligands and have shown robust effects in preclinical models of PD. But is one better than the other? Cass and Peters compared the effects of NTN and GDNF on nigrostriatal dopamine release  in normal rats using microdialysis. Rats received a single unilateral intranigral injection of NTN, GDNF, or vehicle and microdialysis was performed three weeks later to measure striatal release of dopamine. While neither NTN or GDNF had an effect on basal extracellular levels of dopamine, both led to an increase in dopamine overflow evoked by amphetamine. Postmortem tissue levels of dopamine were decreased in the ipsilateral striatum (approximately 20%) and increased in the nigra (approximately 100%) in comparison to the contralateral side in both NTN and GDNF treated animals. Both GDNF and NTN are thought to alter dopamine synthesis, storage, and/or uptake.  While this study is limited in scope it shows comparable effects of NTN and GDNF.

How do other neurotrophic factors, such as MANF and CDNF, compare to GDNF and NTN?