University of California

The Salk Institute for Biological Studies

Other

Signal Pharmaceuticals, Inc.

Jasodhara Ray

Fred Harrison Gage

Jon Asher Wolff

Theodore Friedmann

Michael B Rosenberg

Malcolm Schinstine

Michael D Kawaja

Roger C Guillemin

Dinah W Y Sah

Philippe J Taupin

Minoru Hoshimaru

A method for producing a neuroblast and a cellular composition comprising an enriched population of neuroblast cells is provided. Also disclosed are methods for identifying compositions which affect neuroblasts and for treating a subject with a neuronal disorder, and a culture system for the production and maintenance of neuroblasts.

Method for production of neuroblasts

Conditionally-immortalized human CNS progenitor cell lines are provided. Such cell lines, which may be clonal, may be used to generate neurons and/or astrocytes. Such cell lines and/or differentiated cells may be used for the development of therapeutic agents to prevent and treat a variety of CNS-related diseases. Such cell lines and/or differentiated cells may also be used in assays and for the general study of CNS cell development, death and abnormalities.

Human CNS cell lines and methods of use therefor

The present invention is directed to compositions comprising 1-(&bgr;-D-ribofuranosyl)-1H-1,2,4-triazole compounds and either endogenous or exogenous neurotrophic factors. Methods of using such compounds and compositions are also provided. In one aspect, the invention provides methods of using invention compositions and compounds to enhance neurite outgrowth, neuronal survival and neuronal proliferation in mammalian cells. In a preferred embodiment, a 1-(&bgr;-D-ribofuranosyl)1H-1,2,4-triazole compound is infused directly to a desired situs. In a more preferred embodiment the 1-(&bgr;-D-ribofuranosyl)-1,2,4-triazole compound is administered orally. In another aspect, the invention provides methods of treating a neurological disease in a mammal subject. In a further aspect, the invention provides methods of treating neuronal trauma in a mammal subject.

Pharmaceutical composition comprising ribavirin and growth factors and methods of use

Method for assaying for early gene expression in neuroblasts

The present invention is based on the discovery and isolation of a co-factor for trophic factors. It has been discovered that trophic factors require a co-factor to stimulate and/or potentiate the trophic factor activity and/or specificity. This was clearly identified in low density cells where trophic factors are unable, or at best, at minimal levels, able to proliferate undifferentiated cells without a co-factor. In a particular embodiment of the present invention, there is provided a composition comprising glycosylated cystatin C, (CCg), an FGF co-factor that stimulates proliferation of neural and fibroblast associated undifferentiated cells. The N-glycosylation of cystatin C is required for its activity. Moreover, CCg acts in cooperation with basic fibroblast growth factor (FGF-2) to induce neural progenitor cell proliferation.

Stimulation of cell proliferation by glycosylated cystatin C

A method for producing a neuroblast and a cellular composition comprising an enriched population of neuroblast cells is provided. Also disclosed are methods for identifying compositions which affect neuroblast and for treating a subject with a neuronal disorder, and a culture system for the production and maintenance of neuroblasts.

A novel regulatable retroviral vector in which the v-myc oncogene is driven by a tetracycline-controlled transactivator and a human cytomegalovirus minimal promoter fused to tet operator sequence useful for immortalization of adult neuronal progenitor cells is provided. Regulation of a heterologous Producer cell lines which produce high titers of the recombinant retrovirus are also provided.

Regulatable retrovirus system for genetic modification of cells

Methods of genetically modifying donor cells by gene transfer for grafting into the central nervous system to treat defective, diseased or damaged cells are disclosed. The modified donor cells produce functional molecules that effect the recovery or improved function of cells in the CNS. Methods and vectors for carrying out gene transfer and grafting are described.

Growing community of inventors

San Diego, CA, United States of America

Jasodhara Ray