Gene Therapy for Neurological Disease

Currently, this application lag behind cancer and single-gene metabolic diseases due to  its inherent difficulties.

The major difficulties preventing successful gene-based therapies relate to accessibility of target tissues and the multifactorial nature of many neurological disorders. The central nervous system is generally not amenable to the types of ex vivo interventions successful with blood cells or hepatocytes. Such cells are also difficult to easily target with in vivo approaches. For example, one cannot remove adult neuronal tissue, modify the cells in vitro and reinsert them into the patient because such calls are no longer actively dividing. However, it is possible that Parkinson's disease may be amenable to gene therapy if autologous, actively dividing cells, perhaps bone marrow stem cells or fibroblasts which may be able to successfully populate certain brain regions, can be modified to express the gene for tyrosine hydroxylase. Such cells, when reinfused directly into the brain would then be producing L-dopa or dopamine locally at sufficient concentrations to alleviate the disease phenotype.

Another approach for neurological disease gene therapy is the use of in vivo viral vectors carrying the gene of interest which are targeted to the appropriate region of the CNS. Obviously, for most such diseases, direct injection into the target tissue may be required, as the blood-brain barrier is a substantial obstacle to such an approach. Another problem is that most neural tissues can not be treated with retroviruses which, although they are very efficient at gene delivery, require their target cells to be actively dividing. Therefore, other vector systems, such as herpes simplex or adenoviral vectors are being developed.

Maybe the following Millennium Review can tell you more about neurological gene therapy:

Gene Therapy in the CNS     Gene Therapy, July,2000    (PDF)

The Recent Progress of Study on Gene Therapy in the CNS     Xu Quanyuan, Beijing Institute for Neuroscience