Method of treating melanocortin-4 receptor pathway-associated disorders
Inventors
Van Der Ploeg, Leonardus H. T. • Henderson, Bart • Kuhnen, Peter
Assignees
Charite Universitaetsmedizin Berlin • Rhythm Pharmaceuticals Inc
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Publication Number
US-10960046-B2
Publication Date
2021-03-30
Expiration Date
Abstract
The disclosure is related to a method of treating a disorder, such as Prader Willi Syndrome (PWS), obesity or hyperphagia, in a subject using a melanocortin-4 receptor (MC4R) agonist. Also described is method of treating a subject having a deficiency in the pro-opiomelanocortin (POMC)-MC4R pathway, such as a POMC-null or a PCSK-null subject, using a MC4R agonist.
Core Innovation
The invention relates to a method of treating a disorder in a subject in need thereof by administering an agonist of the melanocortin-4 receptor (MC4R). The treated disorder is characterized by a hypermethylated POMC gene, and the MC4R agonist is defined as a structure of Formula (I).
The MC4R agonist is administered at a daily dosage of about 0.1 mg to about 10 mg. The Formula (I) agonist includes specific definitions for residues A1 through A10 and variable groups R1, R2, R3, R4, R5, m, n, s, and t, with additional structural-variable options described through related formula classes and representative peptide embodiments, including SEQ ID NO:140.
The disclosure links hypermethylated POMC gene status and related POMC-MC4R pathway genetic/epigenetic deficiencies with treatment effects including weight loss, reduced hunger level and food intake, waist circumference, resting energy expenditure, and blood pressure. It also references disorders and indications including Prader-Willi syndrome and POMC-MC4R pathway deficiencies.
Claims Coverage
The independent claim centers on three inventive features: treating a disorder characterized by a hypermethylated POMC gene, administering an MC4R agonist at a specified daily dosage, and using an agonist of a defined Formula (I) structure. Dependent claims further refine the method with additional subject, outcome, and exemplar-agonist limitations.
Treating a disorder characterized by a hypermethylated POMC gene
A method of treating a disorder in a subject in need thereof, where the disorder comprises a disorder characterized by a hypermethylated POMC gene.
Administering an MC4R agonist at about 0.1 mg to about 10 mg daily dosage
Administering an agonist of the melanocortin-4 receptor (MC4R) at a daily dosage of about 0.1 mg to about 10 mg.
MC4R agonist defined by Formula (I) structure
The agonist is a structure of Formula (I): (R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1, with A1 through A10 and R1, R2, R3, R4, R5, m, n, s, and t defined by the specified selection rules.
Overall, claim coverage centers on MC4R agonist treatment for hypermethylated POMC gene disorders using an agonist defined by Formula (I) at about 0.1 mg to about 10 mg daily dosage, with dependent refinements including additional subject and outcome limitations and an exemplar agonist sequence.
Stated Advantages
Weight loss in the treated subject.
Reduced hunger level.
Reduced food intake.
Decreased waist circumference.
Reduced blood pressure.
Documented Applications
Treatment of disorders in a subject characterized by a hypermethylated POMC gene using MC4R agonist therapy.
Treatment of melanocortin-4 receptor pathway-associated obesity/hyperphagia, including Prader-Willi syndrome and POMC-MC4R pathway deficiencies.
Childhood obesity linked to POMC hypermethylation and POMC-MC4R pathway gene defects.
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