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AssigneeBrown University
InventorsAlison R. Amenta, Atilgan Yilmaz, Beth A. McKechnie, Justin R. Fallon
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The present disclosure provides methods for predicting a patient's response to biglycan therapy for diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, for example, due to an unstable dystrophin associated protein complex (DAPC); disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Examples of such diseases include muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, neuromuscular disorders and neurological disorders. This application also provides combination therapeutics, such as a biglycan therapeutic and a utrophin therapeutic.
A method of predicting a patient's response to biglycan therapy, comprising determining whether the patient has a decreased utrophin protein level or activity compared to a reference level, wherein a utrophin protein level or activity that is not decreased relative to the reference level indicates that the patient will likely respond to biglycan therapy.
A method of monitoring an effect of biglycan therapy, comprising measuring the amount of membrane-associated utrophin in a patient receiving biglycan therapy, wherein an increased level of membrane-associated utrophin indicates that the biglycan therapy is effective.
A method of adjusting a patient's dosage of a biglycan polypeptide, comprising administering a first dose of a biglycan polypeptide to a patient, measuring an amount of membrane-associated utrophin in the patient, comparing the amount of membrane-associated utrophin to a predetermined target level, and adjusting the dosage of the biglycan polypeptide responsive to a difference between the measured level and the target level.
A method of measuring the activity of a biglycan polypeptide, comprising administering the biglycan polypeptide to a test cell that expresses utrophin and comparing an amount of membrane-associated utrophin in the test cell with an amount of membrane-associated utrophin in a control cell that did not receive biglycan polypeptide, wherein an increased amount of membrane-associated utrophin in the test cell is indicative of biglycan activity.
11-16. (canceled)
A method of identifying a therapeutic for a biglycan-related condition, comprising administering a test compound to a test cell that expresses utrophin and comparing an amount of membrane-associated utrophin in the test cell with an amount of membrane-associated utrophin in a control cell that did not receive the test compound, wherein an increased amount of membrane-associated utrophin in the test cell indicates that the compound is a therapeutic for a biglycan-related condition.
18-23. (canceled)
A therapeutic composition comprising a biglycan polypeptide and one or more of an anti-inflammatory agent, an agent that increases muscle mass, an agent that increases utrophin mRNA levels, an agent that increases utrophin protein levels, an agent that increases activity of the nNOS system, an agent that promotes repair of the muscle cell membrane, an agent that increases muscle regeneration, an agent that decreases fibrosis, and an antisense agent that promotes exon skipping in dystrophin.
25-34. (canceled)
A method of treating a biglycan-related condition, comprising conjointly administering to a patient in need thereof an effective amount of a composition comprising a biglycan polypeptide and a utrophin polypeptide.
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A method of treating a biglycan-related condition, comprising conjointly administering to a patient in need thereof an effective amount of:
39-52. (canceled)
Dependencies are inferred from the claim text.