Long-term fate of human telencephalic progenitor cells grafted into the adult mouse brain: effects of previous amplification in vitro.

We assessed the developmental potential of human telencephalic progenitor cells, with and without previous amplification in vitro, following grafting into the nonlesioned adult mouse CNS. Cell suspensions, shown to contain neuroepithelium-like and neuroblast-like cells, were injected into the subventricular zone (SVZ) and the striatum. These two regions were selected for comparative studies because one, the SVZ, is mitotically active, whereas the other, the striatum, is mitotically inactive.

A single adenovirus vector mediates doxycycline-controlled expression of tyrosine hydroxylase in brain grafts of human neural progenitors.

Ex vivo gene transfer is emerging as a promising therapeutic approach to human neurodegenerative diseases. By combining efficient methodologies for cell amplification and gene delivery, large numbers of cells can be generated with the capacity to synthesize therapeutic molecules. These cells can then be transplanted into the degenerating central nervous system (CNS).

Adenovirus in the brain: recent advances of gene therapy for neurodegenerative diseases.

Adenovirus is an efficient vector for neuronal gene therapy due to its ability to infect post-mitotic cells, its high efficacy of cell transduction and its low pathogenicity. Recombinant adenoviruses encoding for therapeutical agents can be delivered in vivo after direct intracerebral injection into specific brain areas. They can be transported in a retrograde manner from the injection site to the projection cell bodies offering promising applications for the specific targeting of selected neuronal populations not easily accessible by direct injection, such as the motor neurons in the spinal cord.

Cells of the neuronal lineage play a major role in the generation of amyloid precursor fragments in gelsolin-related amyloidosis.

Gelsolin-related amyloidosis or familial amyloidosis, Finnish type (FAF) (OMIM No105120) is a hereditary amyloid disease caused by a mutation in a precursor protein for amyloid (gelsolin) and characterized by corneal dystrophy and polyneuropathy. In vitro expression of the FAF-mutant (Asp187 --> Asn/Tyr) secretory gelsolin in COS cells leads to generation of an aberrant polypeptide presumably representing the precursor for tissue amyloid. Here, we provide evidence that this abnormal processing results from defective initial folding of the secreted FAF gelsolin due to the lack of the Cys188-Cys201 disulfide bond, normally formed next to the FAF mutation site.

Adenovirus-mediated gene transfer to the central nervous system for Parkinson's disease.

Gene therapy is a potentially powerful approach to the treatment of neurological diseases. The discovery of neurotrophic factors inhibiting neurodegenerative processes and the isolation of genes encoding neurotransmitter synthesizing enzymes provide the basis for current gene therapy strategies for Parkinson's disease. Adenovirus vectors have been shown recently to allow efficient gene transfer to the brain.