Methods and compositions for treatment of disease or injury of the nervous system
Methods for producing new neurons in the brain in vivo are provided according to aspects of the present invention which include introducing NeuroD1 into a glial cell, particularly into a reactive astrocyte or NG2 cell, thereby “converting” the reactive glial cell to a neuron. Methods of producing a neuronal phenotype in a glial cell are provided according to aspects of the present invention which include expressing exogenous NeuroD1 in the glial cell, wherein expressing exogenous NeuroD1 includes delivering an expression vector, such as a viral expression vector, including a nucleic acid encoding the exogenous NeuroD1 to the glial cell.
1. A method of treating stroke, comprising:
administering a therapeutically effective dose of a viral vector comprising a nucleic acid sequence encoding a NeuroD1 protein by intracerebral injection to the brain of an adult mammalian subject; whereby said NeuroD1 protein is expressed in reactive astrocytes, and wherein the number of reactive astrocytes is reduced, and the number of neurons is increased within said subject compared to an untreated subject having a stroke.
2. The method of claim 1 , wherein said nucleic acid sequence comprises a nucleic acid sequence selected from the group consisting of: a nucleic acid sequence encoding SEQ ID NO:2; a nucleic acid sequence encoding SEQ ID NO:4; SEQ ID NO:1; SEQ ID NO:3; and a nucleic acid sequence encoding a protein which has 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or greater, identity to SEQ ID NO: 2 or SEQ ID NO: 4.
3. The method of claim 1 , wherein said NeuroD1 protein comprises the amino acid sequence set forth in SEQ ID NO:2.
4. The method of claim 1 , wherein said subject is a human.
5. The method of claim 1 , wherein said viral vector is an adeno-associated viral vector.