The goal of this proposal is to use liposome-mediated neurotrophin gene transfection to develop efficient and clinically relevant gene therapies to treat traumatic brain injury (TBI). Enhanced expression of neurotrophins produced by liposome-mediated gene transfection may have therapeutic potential for treatment of TBI. A highly focused in vitro research program is an essential prerequisite for the development of in vivo applications.
Aim 1 : Use different cDNA to liposome ratios, concentrations and incubation times to deliver cDNA-liposome complexes in order to evaluate transfection efficiency and duration of transgene expression in primary septo-hippocampal cell cultures.
Aim 2 : Test the potential toxic effects of different types and concentrations of liposomes as well as incubation times on CNS cell cultures.
Aim 3 : Examine the biological activity of neurotrophins and their ability to facilitate recovery from neuronal injury after applying optimized neurotrophin cDNA-liposome complexes into CNS cultures.
Aim 4 : Explore liposome-mediated gene transfection in uninjured and mechanically injured rat brains. We have provided substantial data from coordinated in vitro studies indicating that liposome-mediated transfection of CNS cells can provide increases in mRNA and protein of neurotrophins (NGF, BDNF). We have shown that appropriate transfection protocols, which have minimal toxicity, can produce biologically active neurotrophins and enhance recovery from cholinergic deficiencies. Moreover, we have successfully transfected a reporter gene as well as neurotrophin genes into the uninjured and injured rat brain. The proposed studies represent the first systematic effort to examine the use of non-viral vectors to transfect neurotrophins into CNS cells in order to facilitate recovery from CNS injury. Minimally, the research will provide critical information on the efficiency of liposomal transfection of neurotrophins and essential initial data on the clinical potential of this approach to treat traumatic injury to the central nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035502-03
Application #
2839401
Study Section
Neurology A Study Section (NEUA)
Program Officer
Michel, Mary E
Project Start
1997-12-01
Project End
2002-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
3
Fiscal Year
2000
Total Cost
$175,728
Indirect Cost
Name
Baylor College of Medicine
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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