At the forefront of new devices for neuroprotection
Certain types of sympathetic and sensory neurons are regulated by neurotrophic factors secreted by glial cells. These factors are implicated in neurons survival and development and play a key role in the peripheral and central nervous systems (CNS). Degeneration of dopaminergic neurons has been associated with CNS diseases. Hence, research efforts have been directed towards dissecting the trophic signalling by neurotrophic factors and their receptors in neuronal development and repair. In the frame of GDNF-network, researchers aspired to utilise the properties of the glial cell line-derived neurotrophic factor (GDNF). GDNF belongs to GDNF family ligands also comprising neurturin, persephin and artemin. All members share structural homology and serve as trophic factors activating the transmembrane receptor kinase RET, an important component for neurons survival. The receptor kinase RET activation occurs upon binding of the preformed complex of GDNF ligands with their specific cell-bound co-receptors (GDNF family receptor). Researchers were successful in generating new cell lines for GDNF secretion to be exploited in an encapsulated cell system for implantation into the CNS. Stable clones were initially established from ARPE-19 cells (immortalised retinal pigment epithelial cells). Screening of about 200 clones for increased GDNF secretion resulted in six clones for further evaluation. These were assessed for their secretion potency and stability with good results. The GDNF bioactivity was verified by a cell-based assay. A standard device for experimental implantation into rat brains was then used for encapsulation of the clones giving satisfactory GDNF release levels. The groundbreaking work of GDNF-partners is based on the use of human cells, eliminating zoonosis and the excessive secretion of GDNF, a crucial factor for successful therapy. The application of similar tailor-made devices in animal models will open new channels towards neuroprotection and treatment of neurodegenerative diseases.
