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Developing Gene Silencing for the Study and Treatment of Dystonia

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Technical Report,30 Sep 2014,29 Sep 2017

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The Childrens Hospital of Philadelphia Philadelphia

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Dystonia is a disabling and incurable neurological disorder characterized by twisting movements that cause significant disability. Some forms of dystonia are caused by genetic mutations and, therefore, passed on from generation to generation. The most common form of early onset genetic dystonia is a disease known as DYT1, in which children around age ten develop dystonia, usually in a leg or arm, and over 2 or 3 years spreads to affect all body parts causing substantial disability. There is no cure for DYT1. Therefore, the development of new treatments for DYT1 is a priority in dystonia research. Here, based on prior scientific reports from our research group and other investigators, we hypothesize that we could use two complementary approaches, known as RNA interference or antisense oligonucleotide therapy, to prevent neurons from making the mutated or toxic protein that causes DYT1 dystonia. By doing this in the appropriate brain region, we should be able to reverse the symptoms of the disease. We have already demonstrated that this is possible but using cells growing in a dish in the laboratory, not in living animals. In this project, we aim to answer several specific questions Is this treatment approach helpful and safe What is the area of the brain in which we should inject this RNA interference vector to eliminate the symptoms Are the motor deficits in DYT1 dystonia reversible We propose to use a novel rat model of DYT1 dystonia and infuse antisense oligonucleotides or viral vectors mediating RNA interference to suppress expression of the mutated protein in their brain. They will target different areas of the brain, and we will measure if they are able to reverse known abnormalities that occur in the brain of DYT1 rats, including abnormal motor function. More importantly, we will check if no side effects or toxicity occurs.

Subject Categories:

  • Medicine and Medical Research
  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology

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