Method of dopaminergic and serotonergic neuron formation from neuroprogenitor cells
First Claim
1. A method of forming dopaminergic neurons by contacting in vitro neuroprogenitor cells with an effective amount of FGF-8 and sonic hedgehog (Shh) polypeptide wherein said FGF-8 and Shh polypeptides are encoded by nucleic acid sequences encoding polypeptides comprising SEQ ID NO:
- 4 and SEQ ID NO;
6, respectively.
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Abstract
The present invention relates to neuronal formation and methods of treating diseases characterized by abnormalities in the activity of dopaminergic (DA) and serotonergic (5HT) neurons. In particular, the invention relates to a method of forming serotonergic neurons in vitro by contacting neuroprogenitor cells to an effective amount of native sequence, variants and functional fragments of FGF-4, FGF-8 and Shh. Additionally, disclosed is a method for forming dopaminergic neurons by contacting neuroprogenitor cells to an effective amount of FGF-8 and Shh. Further described are compositions, cell culture compositions and medical devices which contain sufficient amount of FGF-8, Shh or FGF-8, Shh and FGF-4 to stimulate differentiation into dopaminergic or serotonergic neurons, respectively. Further described are methods of using serotoneurgic neurons to treat disorders relating to food intake, hormone secretion, stress response, pain and immune function, sexual activity, cardiovascular function and temperature regulation, in particular, depression, proclivity to suicide, violent aggressive behavior, obsessive-compulsive behavior and anorexia/bulimia and schizophrenia. Further described are methods of using dopaminergic neurons to treat disorders relating postural reflexes, movement and reward-associated behaviors, specifically, Parkinson'"'"'s disease, schizophrenia and drug addiction. Further described is the coadministration of a neuronal survival factor, for example, NGF, CNTF, BDNF, NT-3, NT-4, aFGF, IL-1β, TNFα, IGF-1, IGF-2, TGF-β, TGF-β1 or skeletal muscle extract.
58 Citations
3 Claims
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1. A method of forming dopaminergic neurons by contacting in vitro neuroprogenitor cells with an effective amount of FGF-8 and sonic hedgehog (Shh) polypeptide wherein said FGF-8 and Shh polypeptides are encoded by nucleic acid sequences encoding polypeptides comprising SEQ ID NO:
- 4 and SEQ ID NO;
6, respectively. - View Dependent Claims (3)
- 4 and SEQ ID NO;
-
2. A composition comprising a pharmaceutically-acceptable carrier and an effective amount of the FGF-8 polypeptide of SEQ ID NO:
- 4 and the Shh polypeptide of SEQ ID NO;
6 to stimulate differentiation of neuroprogenitor cells into dopaminergic neurons.
- 4 and the Shh polypeptide of SEQ ID NO;
Specification