Weidong Xiong, MD
Research Scientist I
Weidong Xiong, MD is a postdoctoral researcher at the Board of Governors Gene Therapeutics Research Institute at Cedars-Sinai. He previously served as a postdoctoral research associate at the Molecular Medicine and Gene Therapy Unit of the University of Manchester in the United Kingdom.
Dr. Xiong received his medical degree from Henan Medical University. After practicing general medicine and cardiology for eight years in the first teaching hospital of Henan Medical University, he joined the National Laboratory of Molecular Virology and Genetic Engineering, Institute of Virology in Beijing, where he earned his master's degree.
Dr. Xiong's current research project relates to the development of a high capacity adenovirus vector system that will deliver neuroprotective molecules in Parkinson's disease models. He is using the latest generation tetracycline-sensitive reverse-transactivator alone and in combination with Tet-repressor, aiming to establish maximal induction with minimal leakiness of therapeutic transgene expression under the control of a strong promoter for pre-clinical gene therapy.
Specific degeneration of the nigrostriatal dopamine (DA) neurons of the substantia nigra pars compacta and the resulting loss of nerve terminals accompanied by DA deficiency in the striatum are responsible for most of the movement disturbances associated with Parkinsonism (i.e., muscle rigidity, akinesia and resting tremor) observed in Parkinson's disease. Recent developments in viral vectors capable of providing high levels and long-term transgene expression in the brain have led to the pursuit of two strategies in gene therapy for the treatment of Parkinson's disease. One is the local production of dopamine in the striatum, achieved by inducing the expression of dopamine-synthesizing enzymes. The second strategy entails the expression of neurotrophic factors or brain vesicular monoamine transporter in the striatum or the substantia nigra to slow the degeneration of dopamine neurons.
Concepts of neuroprotection and restoration of the nigrostriatal pathway will become important themes for future genetic treatment strategies for Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF) is currently the most effective neurotrophic factor that has been intensively studied and shown to have a specific trophic effect in the dopaminergic neurons. The latest generation adenovirus vectors (also named gutless vectors) offer several advantages in relation to the first generation vectors, such as not encoding for any viral proteins (thus avoiding putative interference in transgene expression), having a large cloning capacity of up to 32kb to encode therapeutic or regulatory transgenes and being capable of long-term transgene expression. These characteristics make them very attractive for clinical trials and promising tools for treatment of diseases like Parkinson's disease.
