GDNF (Including neurturin)

The discovery of GDNF as a potent trophic factor for dopamine neurons has led to more than two decades of research on the cellular and molecular properties of the protein, its receptors and identification of other family members. GDNF and the closely related trophic factor NTRN have the potential to revolutionize the treatment of Parkinson’s disease and other neurodegenerative disorders. The field is now in a challenging era, where three Phase 1 clinical trials have yielded encouraging results, while the four Phase 2 studies have been failed to demonstrate a significant level of improvement over placebo controls. Analysis of the clinical trials strongly suggests that efficacious therapeutic approaches require site-specific delivery of trophic factors using methodology to optimize target tissue distribution and initiation of treatment in the first years after diagnosis. Because of significant placebo-associated benefits, therapeutic efficacy must be assessed in double-blinded, randomized, placebo-controlled clinical trials.