Finding effective methods to deliver the genetic " blueprints " of the correct and functional protein or, even better, the " DNA repairing kit " able to do the job in situ, remains a major challenge, despite the fact that gene therapy is already used in different diseases. The most straightforward approach to correct the main culprit in hemoglobinopathies-the imbalance between the amounts of alpha-like globins/beta-like globins-will need to target directly the gene structure or their regulatory elements in order to obtain a sustained therapeutic effect. (2005) HSV-mediated gene transfer of vascular endothelial growth factor to dorsal root ganglia prevents diabetic neuropathy.Hemoglobinopathies, such as β-thalassemia and sickle cell disease (SCD), are among the most common congenital diseases in the world, with high mortality and morbidity rates. Ann Neurol 59:843-51Ĭhattopadhyay, M Krisky, D Wolfe, D et al. (2006) Tumor necrosis factor-alpha contributes to below-level neuropathic pain after spinal cord injury. Peng, Xiang-min Zhou, Zhi-gang Glorioso, Joseph C et al. Gene Ther 16:453-4Ĭhattopadhyay, Munmun Mata, Marina Fink, David J (2008) Continuous delta-opioid receptor activation reduces neuronal voltage-gated sodium channel (NaV1.7) levels through activation of protein kinase C in painful diabetic neuropathy. Glorioso, J C Fink, D J (2009) Gene therapy for pain: introduction to the special issue.
#DAVID FINK GENE THERAPY SWEDISH COMPANY TRIAL#
Wolfe, D Mata, M Fink, D J (2009) A human trial of HSV-mediated gene transfer for the treatment of chronic pain. (2011) Gene therapy for pain: results of a phase I clinical trial. Mol Cell Neurosci 48:29-37įink, David J Wechuck, James Mata, Marina et al. (2011) Rho GTPase regulation of ýý-synuclein and VMAT2: implications for pathogenesis of Parkinson's disease. Zhou, Zhigang Kim, Jeeyong Insolera, Ryan et al. Wolfe, Darren Mata, Marina Fink, David J (2012) Targeted drug delivery to the peripheral nervous system using gene therapy. (2012) Transgene-mediated expression of tumor necrosis factor soluble receptor attenuates morphine tolerance in rats. (2013) Full-length membrane-bound tumor necrosis factor-? acts through tumor necrosis factor receptor 2 to modify phenotype of sensory neurons. Wu, Zetang Wang, Shiyong Gruber, Sandy et al. To create and test novel HSV-based vectors in models of neuropathic, inflammatory, and cancer pain. To systematically evaluate biodistribution and biosafety of the recombinant enkephalin expressing vector in rodents. To test the effect of prior immunity on vector transduction, the potential of the recombinant vector to reactivate latent virus, and to study the level and kinetics of the anti-nociceptive response following repeated vector re-inoculation. To construct a vector with a regulatable """"""""switch"""""""" to control vector-mediated enkephalin expression in vivo. To define the duration and dose-response characteristics of the vector-mediated analgesic effect.
These studies are designed to overcome the barriers that stand between preclinical proof-of-principle experiments and the development of a treatment for the human disease, and to create novel vectors to enhance gene therapy for specific types of pain.
#DAVID FINK GENE THERAPY SWEDISH COMPANY SERIES#
In response to the RFA, we propose a series of studies to investigate the hypothesis that HSV-mediated gene transfer to the DRG may be used to treat chronic pain. The preclinical data for this novel approach to the treatment of pain is compelling. The effect is local, synergistic with morphine, and persists despite tolerance to morphine. We have demonstrated that HSV based vectors can be used to transduce neurons of the DRG to achieve an antinociceptive effect in models of inflammatory pain, neuropathic pain, and pain resulting from tumor in bone. Herpes simplex virus (HSV) naturally targets with high efficiency to neurons of the dorsal root ganglion (DRG) from peripheral inoculation. But chronic pain, often disabling and refractory to treatment, represents a difficult medical problem with enormous societal impact. Pain is a subjective experience with affective and cognitive components, an """"""""unpleasant sensory and emotional experience associated with actual or potential tissue damage that serves an essential role in alerting an individual to potentially harmful stimuli in the environment"""""""".
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