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Grunblatt, E., Mandel, S., Jacob-Hirsch, J., Zeligson, S., Amariglo, N., Rechavi, G., Li, J., Ravid, R., Roggendorf, W., Riederer, P. and Youdim, M. B. (2004) Gene expression profiling of Parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. Journal of Neural Transmission, 111, 1543-1573. doi:10.1007/s00702-004-0212-1

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• TITLE: Can population genomics guide future therapeutic gene transfer strategies for Parkinson’s disease?

  AUTHORS: Massimo S. Fiandaca, Robert M. Padilla, Ishmeal Conteh, Howard J. Federoff

  KEYWORDS: Biomarkers; Functional Imaging; Gene Therapy; Parkinson’s Disease; Population Genomics; Prodromal Phase

  JOURNAL NAME: Open Journal of Genetics, Vol.3 No.2A, June 26, 2013

  ABSTRACT: Medical and surgical therapies for patients with Parkinson’s disease (PD) are typically considered and initiated upon development of clinical signs, especially therapeutic gene transfer therapies. Early clinical trials delivering transgenes within the brains of PD patients have confirmed their safety and suggested mild to moderate efficacy. Confirmatory phase III trials have yet to be undertaken with any of the current treatment regimens. During the development of PD gene therapy, mapping of the human genome was finalized and provides major insights into the normal and pathogenic genetic variabilities of populations. Genome wide association studies (GWAS) have expanded the genetic defects and risk factors accompanying clinical PD. Advanced genomic investigations may allow asymptomatic individuals with a high risk of developing PD, and evident presymptomatic nigrostriatal deficiencies, to consider early treatment approaches. Herein we propose that certain genomically and clinically defined PD patients may provide unique opportunities for testing neuronotrophic gene therapy in a pathobiological environment that is antecedent to overt motoric dysfunction. Such an approach may finally allow testing of the disease-altering capabilities of therapeutic gene transfer in PD.