Methods for treating apolipoprotein E4-associated disorders
View Patent ↗The present disclosure provides a method of increasing the functionality of a GABAergic interneuron in the hilus of the hippocampus of an individual having at least one apolipoprotein E4 (apoE4) allele. The method generally involves reducing tau levels in the interneuron.
1. A method of increasing the functionality of a GABAergic interneuron in the hilus of the hippocampus of an individual having at least one apolipoprotein E4 (apoE4) allele, the method comprising administering to the individual a tau-specific interfering nucleic acid that binds to a tau target and reduces the level of a tau polypeptide in the GABAergic interneuron, wherein the tau target is a contiguous stretch of at least 10 nucleotides of 5596-5807 of SEQ ID NO:2, wherein the tau-specific interfering nucleic acid is coupled to a carrier molecule that provides targeted delivery of the tau-specific interfering nucleic acid to the GABAergic interneuron.
2. The method of claim 1 , wherein said tau-specific interfering nucleic acid is encoded by a nucleotide sequence operably lined to a neuron-specific transcriptional control element that is active in the GABAergic interneuron, wherein the nucleotide sequence is present in a recombinant expression vector.
3. The method of claim 1 , wherein said administering is via a local route of administration.
4. The method of claim 3 , wherein said administering is via intracranial administration.
5. The method of claim 1 , wherein said increasing the functionality of a GABAergic interneuron results in an increase in cognitive function in the individual as determined by a cognitive assessment.
6. The method of claim 5 , wherein said cognitive function is learning or memory.
7. The method of claim 1 , wherein the carrier molecule is an antibody that specifically binds to the GABAergic interneuron.