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Publication Number
US-12139729-B2
Publication Date
2024-11-12
Expiration Date
Abstract
A cyclic polypeptide, derivative or analogue thereof, comprising an amino acid sequence derived from the C-terminus of acetylcholinesterase (AChE), or a truncation thereof.
Core Innovation
The invention relates to cyclic polypeptides and derivatives derived from the C-terminus of tailed acetylcholinesterase (AChE) for treating neurodegenerative disorders, including Alzheimer's disease. Cyclic examples referenced include cyclic T14, CT14, and NBP14, and the description links non-classical actions of AChE-derived peptides to a trophic-toxic mechanism associated with pathological calcium (Ca2+) influx.
The cyclic polypeptides are proposed to act as selective antagonists and/or inert allosteric modulators at the 517 nicotinic acetylcholine receptor (517 nAChR). They are described as competing with linear T14/T30 and b2-amyloid to prevent pathological Ca2+ influx and downstream toxicity, with potency/affinity contrasted with galanthamine, which is mentioned as Reminyl.
The document further describes supporting findings and outcomes associated with the mechanism, including protection from toxicity caused by Ab2, T14, and T30, reduction of APP and Ab242 release, and binding displacement at an ivermectin-sensitive allosteric site using [3H] ivermectin. In vivo findings are described as behavioral improvement in a hemi-parkinsonism setting, and the document also references representative sequences (SEQ ID No: 4) and related cyclic peptide sequence identifiers.
Claims Coverage
The partial content provides one independent claim. It centers on administering a therapeutically effective amount of a cyclic polypeptide defined by Seq ID No: 4 to treat or ameliorate Alzheimer's disease.
Treating or ameliorating Alzheimer's disease by administering a cyclic polypeptide defined by Seq ID No: 4
A method of treating or ameliorating Alzheimer's Disease in a subject by administering to a subject in need of such treatment a therapeutically effective amount of the cyclic polypeptide according to Seq ID No: 4.
Across the provided independent claim, coverage is directed to therapeutic administration of a cyclic polypeptide specified by Seq ID No: 4 for treating or ameliorating Alzheimer's disease.
Stated Advantages
Prevention of pathological Ca2+ influx and downstream toxicity through selective antagonism/inert allosteric modulation at the 517 nAChR.
Protection from toxicity associated with Ab2, T14, and T30.
Reduction of APP and Ab242 release.
Improvement of behavioral outcomes in a hemi-parkinsonism setting (in vivo described).
Documented Applications
Treatment or amelioration of Alzheimer's Disease in a subject by administering a cyclic polypeptide according to Seq ID No: 4.
Application to neurodegenerative disorders more generally, including Alzheimer's disease and Parkinson's disease, as described in the document context.
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