Method for neural stem cell differentiation using 5ht1a agonists
AssigneePsychiatric Genomics, Inc.
InventorsPrithi Rajan, C. Anthony Altar
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Abstract
Abstract of Disclosure The present invention relates to a method for differentiating a neural stem cell into a neuronal cell such as a neuroblast or a neuron in vitro or in vivo. Particularly, the invention provides for a method for neural stem cell differentiation by contacting the neural stem cell with a 5HT1A ligand or agonist.
Claims47
A method for preparing a population of mammalian neural cells enriched with neuronal cells comprising the step of exposing a population of neural stem cells comprising neural stem cells with a 5HT1A agonist in an amount and at a frequency of exposure sufficient to induce differentiation of said stem cells to express preferentially the neuronal phenotype.
A method of treating a CNS or PNS disorder characterized by neuronal damage or depletion in an individual suffering from said damage or depletion the method comprising administering to said individual a composition comprising a 5HT1A agonist, in an amount effective to induce differentiation of neural stem cells of said individual preferentially into neurons, thereby alleviating said damage or depletion.
A method of treating a CNS or PNS disorder characterized by neuronal damage or depletion in an individual suffering from said damage or depletion the method comprising implanting to said individual a composition comprising a population of neurons that have been differentiated in vitro from human neural stem cells by a method comprising exposure of said stem cells to a 5HT1A agonist in an amount effective to alleviate said damage or depletion.
A method for identifying a compound that affects differentiation of mammalian neural stem cells comprising:
- (a) exposing a first population comprising neural stem cells in vitro to a 5HT1A agonist in an amount sufficient to induce differentiation of said cells preferentially into neurons;
- (b) exposing a second population comprising neural stem cells in vitro to a 5HT1A agonist in an amount sufficient to induce differentiation of said cells preferentially into neurons;
- (c) either before or immediately after the exposure in said step (b),further exposing said second population to a test substance;
- (d) comparing the proportion of stem cells differentiated into neurons in step (a) to the proportion of stem cells differentiated into neurons after step (c);
- and (e)concluding that said test compound affects differentiation based on the difference between said proportions.
A method for identifying lead compounds for treatment of CNS disorders characterized by neuronal damages or depletion, comprising:
- (a) culturing in the presence of a test compound a first population of mammalian neural cells resulting from differentiation of mammalian neural stem cells by exposure to a 5HT1A agonist to express predominantly the neuronal phenotype;
- (b) culturing in the absence of said test compound a second population of neural cells resulting from differentiation of mammalian neural stem cells by exposure to a 5HT1A agonist to express predominantly the neuronal phenotype;
- (c) assessing in said first and second differentiated neural cells population, the level of expression of a gene, the expression of which is up- or down-regulated in cells or tissue of individuals afflicted with or at risk for said disorder and wherein said up- or down- regulation correlates with said disorder;
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- (d) determining whether said test compound is a lead compound depending on whether presence of said compound results in a difference in the expression of said gene between said second and said first differentiated neural cell population.
A method for identifying new drug candidates for treatment of CNS disorders characterized by neuronal damages or depletion, comprising:
- (a) culturing in the presence of a test compound a first population of mammalian neural cells resulting from differentiation of mammalian neural stem cells by exposure to the 5HT1A agonist to express predominantly the neuronal phenotype;
- (b) culturing in the absence of said test compound a second population of neural cells resulting from differentiation of neural stem cells by exposure to the 5HT1A agonist to express predominantly the neuronal phenotype;
- (c) assessing in said first and second differentiated neural cells population, the level of expression of a gene the expression of which is up- or down-regulated in cells or tissue of individuals afflicted with or at risk for said disorder and wherein said up- or down- regulation correlates with said disorder;
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- (d) determining whether said test compound is a new drug candidate depending on whether presence of said compound results in a difference in the expression of said gene between said second and said first differentiated neural cell population.
Dependencies are inferred from the claim text.