Tapan Behl*, Ishnoor Kaur, Arun Kumar, Vineet Mehta, Gokhan Zengin and Sandeep Arora Pages 207 - 222 ( 16 )
The limitations of conventional treatment therapies in Parkinson’s disorder, a common neurodegenerative disorder, lead to the development of an alternative gene therapy approach. Multiple treatment options targeting dopaminergic neuronal regeneration, production of enzymes linked with dopamine synthesis, subthalamic nucleus neurons, regulation of astrocytes and microglial cells and potentiating neurotrophic factors, were established. Viral vector-based dopamine delivery, prodrug approaches, fetal ventral mesencephalon tissue transplantation and dopamine synthesizing enzyme encoding gene delivery are significant therapies evidently supported by numerous trials. The review primarily elaborates on the significant role of glial cell-line derived neurotrophic factor in alleviating motor symptoms and the loss of dopaminergic neurons in Parkinson’s disease. Neuroprotective and neuroregenerative effects of GDNF were established via preclinical and clinical study outcomes. The binding of GDNF family ligands with associated receptors leads to the formation of a receptor-ligand complex activating Ret receptor of tyrosine kinase family, which is only expressed in dopaminergic neurons, playing an important role in Parkinson’s disease, via its association with the essential protein encoded genes. Furthermore, the review establishes delivery aspects, like ventricular delivery of recombinant GDNF, intraparenchymal and intraputaminal delivery using infusion catheters. The review highlights problems and challenges of GDNF delivery, and essential measures to overcome them, like gene therapy combinations, optimization of delivery vectors, newer targeting devices, motor symptoms curbing focused ultrasound techniques, modifications in patient selection criteria and development of novel delivery strategies based on liposomes and encapsulated cells, to promote safe and effective delivery of neurotrophic factor and establishment of routine treatment therapy for patients.
Neurodegenerative disorder, dopaminergic neuronal regeneration, subthalamic nucleus neurons, viral vector, fetal ventral mesencephalon, glial cell-line derived neurotrophic factor, ret receptor.
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, Government College of Pharmacy, Shimla, Department of Biology, Faculty of Science, Selcuk University Campus, Konya, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab