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- W843450355 abstract "Neurodegenerative disorders are characterized by a progressive cell-death in the brain, and loss of different functions in the patient. Today, there are no cures for any of the various diseases. Parkinson's disease is a neurodegenerative disorder with a prevalence of 0.1% and the first symptoms usually start to appear between 50-60 years of age with rigidity, tremor, bradykinesia and postural abnormalities. Even though the reason for the development is not fully understood, the pathophysiology of the disease has been well documented. ?Sere is a progressive loss of dopamine-producing cells in substantia nigra in the midbrain, resulting in a significant decline of dopamine levels in the striatum and a disturbed motoric function. ?Se most common treatment today is oral intake of levodopa, the rate-limiting enzyme in the dopamine synthesis pathway, however the effects of the drug becomes limited over time and hence, there is a need for alternative therapy. Instead of using fetal human tissue for transplantation, with both logistical and ethical dilemmas, ex vivo gene therapy holds great promise for treatment of different neurodegenerative disorders. Ex vivo gene therapy is a combination of cell transplantation and genetic engineering, with the aim of restoring lost neurotransmitters, such as dopamine, or to transfer neurotrophic factors to stimulate cell survival in a damaged or injured brain. In the present thesis, I have genetically modified primary astrocytes of both rodent and human origin with lentiviral vectors in order to evaluate the potential of the cells to provide long-term transgene expression following transplantation to the rat brain. Astrocytes are a type of glial cells in the brain attributed various functions, and have been explored in several studies to be used as cellular vehicles in ex vivo gene delivery to the central nervous system. Compared to previous studies were astrocytes have been genetically modified in vitro using other viralbased vectors, I have shown in my work that lentivirally transduced astrocytes have the capacity to express the transgene product at significant levels for up to at least 12 weeks after grafting to the rat brain. However, before moving towards clinical trials using genetically modified astrocytes, the vector system has to be further developed in order to be able to regulate the transgene expression, even after the cells have been integrated within the host brain." @default.
- W843450355 created "2016-06-24" @default.
- W843450355 creator A5062448705 @default.
- W843450355 date "2005-01-01" @default.
- W843450355 modified "2023-09-23" @default.
- W843450355 title "Astrocytes as Cellular Vehicles in Ex Vivo Gene Therapy Studies to the Rat Brain" @default.
- W843450355 hasPublicationYear "2005" @default.
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