SEQUENCE LISTING IN ELECTRONIC FORMAT

The present application is being filed along with an Electronic Sequence Listing as an ASCII text file via EFS-Web. The Electronic Sequence Listing is provided as a file entitled ZNTH001001C1SEQLIST.txt, created and last saved on Jun. 10, 2020, which is 7,372 bytes in size. The information in the Electronic Sequence Listing is incorporated herein by reference in its entirety.

TECHNICAL FIELD

The present disclosure relates to an inhibitor against amyloid β accumulation and/or aggregation and, more particularly, to compositions and methods for inhibiting amyloid β accumulation and/or aggregation by concurrently introducing Nurr1 and Foxa2 genes to a mammal.

BACKGROUND OF THE INVENTION

Alzheimer's disease is a chronic neurodegenerative disease having symptoms most commonly including memory loss, difficulties with language, cognitive impairment, etc.

Alzheimer's disease is neuropathologically characterized by the presence of plaques in brain cells, nervous tissues, and vessels, neurofibrillary tangles (NFTs), the presence of amyloid β responsible for the formation of amyloid plaques, the loss of synapses, etc. The cause for most Alzheimer's cases still remains unknown. Further, there has been no cure for Alzheimer's disease, thus far. Alzheimer's disease accounts for the most common cases of dementia, acting as a main cause of death, like cardiovascular diseases and cancer. The frequency of Alzheimer's disease is predicted to increase with the average lifespan of humans.

In addition, an enormous expense is required for managing and treating Alzheimer's disease, with the patients suffering from considerable mental anguish. Therefore, there is a need for effective method for preventing and treating Alzheimer's disease.

SUMMARY OF THE INVENTION

Leading to the present disclosure, the research conducted by the present inventors resulted in the experimental finding that introduction and expression of Nurr1 and Foxa2 genes in brain cells inhibits the accumulation and/or aggregation of amyloid β. Particularly, when a Nurr1 gene was expressed together with a Foxa2 gene rather than alone, the two genes were found to have a potent synergistic effect of inhibiting amyloid β accumulation and/or aggregation.

Therefore, one embodiment of the present disclosure provides an amyloid β accumulation and/or aggregation inhibitor comprising a vector carrying both a Nurr1 gene and a Foxa2 gene.

Another embodiment of the present disclosure provides an amyloid β accumulation and/or aggregation inhibitor comprising neurons, neuronal stem cells or neuronal precursor cells, or glia, which all have both a Nurr1 gene and a Foxa2 gene introduced thereinto.

Still another embodiment of the present disclosure provides an inhibitor against the expression of inflammasomes, complements, chemokines (CCL3 and CCL4), inflammatory cytokines (IL-1β and TNF-α), apolipoprotein E (ApoE), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), or asparaginyl endopeptidase (AEP), the inhibitor comprising a vector carrying both a Nurr1 gene and a Foxa2 gene.

Yet another embodiment of the present disclosure provides an inhibitor against the expression of inflammasomes, complements, chemokines (CCL3 and CCL4), inflammatory cytokines (IL-1β and TNF-α), apolipoprotein E (ApoE), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), or asparaginyl endopeptidase (AEP), the inhibitor comprising neurons, neuronal stem cells or neuronal precursor cells, or glia, which all have both a Nurr1 gene and a Foxa2 gene introduced thereinto.

Still a further embodiment of the present disclosure provides a composition for preventing or treating a disease caused due to amyloid β accumulation and/or aggregation, the composition comprising a vector carrying both a Nurr1 gene and a Foxa2 gene.

Another embodiment of the present disclosure provides a composition for preventing or treating a disease caused due to amyloid β accumulation and/or aggregation, the composition comprising neurons, neuronal stem cells or neuronal precursor cells, or glia, which all have both a Nurr1 gene and a Foxa2 gene introduced thereinto.

One other embodiment of the present disclosure provides a composition for inhibiting cellular senescence caused due to amyloid β accumulation and/or aggregation, the composition comprising a vector carrying both a Nurr1 gene and a Foxa2 gene.

Another embodiment of the present disclosure is a method of treating a patient suffering from Alzheimer's disease, comprising administering to the patient a therapeutically effective dose of a composition comprising a vector carrying both a Nurr1 gene and a Foxa2 gene.

Another embodiment of the present disclosure is a method of treating a patient suffering from Alzheimer's disease, comprising administering to the patient a therapeutically effective dose of a composition comprising a vector carrying a Nurr1 gene and a second vector carrying a Foxa2 gene.

