CD44 splice variants in neurodegenerative diseases
Inventors
Pinner, Elhanan • Laudon, Moshe • Zisapel, Nava
Assignees
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Publication Number
US-9018180-B2
Publication Date
2015-04-28
Expiration Date
Abstract
There is provided a method of treating or preventing a neurodegenerative disease, which includes administration of a composition that includes a reagent capable of modulating expression of ribonucleic acid (RNA) encoded by a nucleic acid, wherein the nucleic acid is selected from a group that includes a contiguous nucleotide sequence being at least 90% homologous to at least 20 nucleotides of: SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, or any combination thereof. There is further provided a method of treating or preventing a neurodegenerative disease, which includes administration of a composition that includes a reagent capable of modulating expression and/or activity of a polypeptide, wherein the sequence of the polypeptide is selected from a group that includes a contiguous amino acid sequence being at least 90% homologous to at least 10 amino acid of: SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, or any combination thereof.
Core Innovation
The invention is directed to CD44 splice variants encoded by nucleic acids and corresponding polypeptides, and to their use as biomarkers and therapeutic targets in neurodegenerative diseases. The described nucleic acid and polypeptide targets include CD44 splice variants defined by specified SEQ ID NO regions with stated homology thresholds, and patient samples are used to detect nucleic acids and/or polypeptides corresponding to CD44 splice variants for diagnosis and monitoring.
A method of treating or inhibiting a neurodegenerative disease selected from Alzheimer's disease and ALS is described as comprising administration of a composition containing a reagent capable of reducing expression of RNA encoded by a nucleic acid. The nucleic acid is selected from contiguous nucleotide sequences that are at least 90% homologous to at least 20 nucleotides within specified coordinate regions of SEQ ID NO: 1, 3, 5, 7, or any combination thereof, and the reagent comprises one or more polynucleotides capable of hybridizing with the nucleic acid, a small molecule entity (SME), or combinations thereof.
Functional support includes localization of CD44 in Alzheimer’s disease hippocampus and modulation of CD44 alternative splicing, in which ERK-MAP and PKC pathway modulation is associated with changes affecting CD44 splice variants. The treatment concept is connected to reducing expression of CD44-variant–encoded RNAs and/or modulating CD44-variant polypeptide expression and activity, with documented examples including CD44S, CD44V3, CD44V6, CD44V10, and CD44V7 in described contexts.
Claims Coverage
The partial content supports one independent claim family member directed to treating or inhibiting neurodegenerative disease by administering a reagent that reduces expression of CD44-variant–encoded RNA. The independent claim contains two main inventive features.
Targeting RNA encoded by SEQ ID coordinate regions with high-homology contiguous nucleotide sequences
A nucleic acid selected from contiguous nucleotide sequences being at least 90% homologous to at least 20 nucleotides of specified coordinate regions of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, or any combination thereof.
Reducing RNA expression using hybridizing polynucleotides and/or a small molecule entity
Administration of a composition comprising a reagent capable of reducing expression of RNA encoded by the selected nucleic acid, where the reagent comprises one or more polynucleotides capable of hybridizing with the nucleic acid, a small molecule entity (SME), or combinations thereof.
Overall, the claim coverage centers on reducing RNA expression of CD44-variant–encoded nucleic acids defined by specified high-homology coordinate regions, using hybridizing polynucleotides and/or an SME as the reducing-expression reagent.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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