Promoting Neurotrophic Processes

Certain cellular processes operate to enhance neuronal health and development, and may function in reaction to the progressive neurodegeneration observed in PD. These processes have been identified as therapeutic targets with the potential of countering PD pathogenic processes.

Strategies to target neurogenic pathways focus on cell replacement therapy utilizing stem cells. The neurotrophic factors GDNF, Neurturin, CDNF, FGF20, BDNF, artemin, and pleiotrophin all have potential to be utilized though direct infusion or gene therapy delivery methods. Clearer understanding of their mechanism of neuroprotection in DA neurons will aid in developing translational therapies.

• GDNF: Clinical trials for GDNF have used direct brain infusion. These trials have shown ambiguous but at times promising results. Issues of trophic factor delivery need to be addressed to improve the chances of a beneficial therapy. Additional GDNF delivery approaches under investigation include intraparenchymal implantation of GDNF-producing cells as well as designing GDNF that can cross the blood-brain barrier.
• Neurturin: A Phase II trial of CERE-120 (Ceregene Inc., funded in part by MJFF) demonstrated no difference between the experimental and control groups.