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Gene therapy in the CNS: intracerebral grafting of genetically modified cells
F H Gage1, M B Rosenberg, M H Tuszynski
1Department of Neurosciences, University of California at San Diego, La Jolla 92093.
Abstract:
Grafting cells to the CNS has been suggested and applied as a potential approach to CNS therapy through the selective replacement of cells lost as a result of disease or damage. Independently, studies aimed at direct genetic therapy in model systems have recently begun to suggest conceptually new approaches to the treatment of several kinds of human genetic disease, especially those caused by single gene enzyme deficiencies. We suggest that a combination of these two approaches, namely the graftment into the CNS of genetically modified cells, may provide a new approach toward the restoration of some functions in the damaged or diseased CNS. We present evidence for the feasibility of this approach, including a description of some current techniques for mammalian cell gene transfer and CNS grafting, and several possible approaches to clinical applications. Specifically, we report that fibroblasts, genetically modified to secrete NGF by infection with a retroviral vector and implanted into the brains of rats with a surgical lesion of the fimbria-fornix, prevented the degeneration of cholinergic neurons that would die without treatment.
Insights
Combining cell grafting and genetic modification offers a novel therapy for central nervous system (CNS) damage. Genetically engineered cells secreting nerve growth factor (NGF) protected neurons in a rat brain injury model.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Gene Therapy
Background:
- Cellular grafting and genetic therapy are potential CNS treatments.
- Existing methods aim to replace lost cells or correct genetic defects.
Purpose of the Study:
- To explore the combined approach of grafting genetically modified cells into the CNS.
- To investigate the feasibility of restoring CNS function through this combined strategy.
Main Methods:
- Genetically modifying rat fibroblasts to secrete nerve growth factor (NGF) using retroviral vectors.
- Implanting these modified fibroblasts into the brains of rats with fimbria-fornix lesions.
- Assessing the survival of cholinergic neurons post-implantation.
Main Results:
- Genetically modified fibroblasts successfully secreted NGF.
- Implantation of NGF-secreting fibroblasts prevented the degeneration of cholinergic neurons.
- This approach demonstrated feasibility in a rodent model of CNS damage.
Conclusions:
- Combining CNS grafting with genetic modification is a promising therapeutic strategy.
- This approach can restore function by delivering therapeutic proteins like NGF.
- Further research into clinical applications for CNS disorders is warranted.
