Compositions and methods for diagnosing and treating dystonia
AssigneeDuke University
InventorsNicole Calakos, Zachary Caffall, Connor King
Life of this patent
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Abstract
Disclosed herein are compositions, kits, and methods for identifying protein, miRNA, or metabolite biomarkers for dystonia, for treating a subject having a dystonia, for selecting a subject for a clinical trial, for selecting a therapeutic agent, for treatment of dystonia in a subject, for classifying a subject having dystonia, and for predicting responsiveness to a dystonia treatment.
Claims23
A method of treating dystonia in a subject, comprising administering to the subject one or more therapeutic agents when one or more dystonia biomarkers in the subject is aberrant compared to a reference level,
- wherein the one or more dystonia biomarkers comprises
- (i) a protein selected from List-A1, List-A2, List-A3, List-A4, List-B1, List-B2, List-B3, List-C1, List-C2, List-C3, List-D1, List-D2, List-D3, List-E1, List-E2, List-E3, List-F1, List-F2, List-F3, List-G1, List-G2, List-G3, TABLE 4, TABLE 5, TABLE 6, TABLE 7, TABLE 8, TABLE 9, TABLE S1, TABLE S3, TABLE S4, TABLE S5, TABLE S6, TABLE S7, or a combination thereof;
- (ii) an miRNA selected from List-MR1, TABLE 2, TABLE 3, or a combination thereof;
- or
- (iii) a metabolite selected from List-ML1, or a combination thereof.
A method of treating dystonia in a subject, comprising administering to the subject an amount of one or more therapeutic agents, wherein the amount of the one or more therapeutic agents is increased or reduced from a preliminary dosage amount when one or more dystonia biomarkers in the subject is aberrant compared to a reference level,
- wherein the one or more dystonia biomarkers comprises
- (i) a protein selected from List-A1, List-A2, List-A3, List-A4, List-B1, List-B2, List-B3, List-C1, List-C2, List-C3, List-D1, List-D2, List-D3, List-E1, List-E2, List-E3, List-F1, List-F2, List-F3, List-G1, List-G2, List-G3, TABLE 4, TABLE 5, TABLE 6, TABLE 7, TABLE 8, TABLE 9, TABLE S1, TABLE S3, TABLE S4, TABLE S5, TABLE S6, TABLE S7, or a combination thereof;
- (ii) an miRNA selected from List-MR1, TABLE 2, TABLE 3, or a combination thereof;
- or
- (iii) a metabolite selected from List-ML1, or a combination thereof.
A method of selecting a subject for a clinical trial, the method comprising
- a) measuring one or more dystonia biomarkers in the subject from a biological sample obtained from the subject, and
- b) enrolling the subject in the clinical trial when the one or more dystonia biomarkers in the subject is aberrant compared to a reference level, or not enrolling the subject in the clinical trial when the one or more dystonia biomarkers in the subject is not aberrant compared to a reference level,
- wherein the one or more dystonia biomarkers comprises
- (i) a protein selected from List-A1, List-A2, List-A3, List-A4, List-B1, List-B2, List-B3, List-C1, List-C2, List-C3, List-D1, List-D2, List-D3, List-E1, List-E2, List-E3, List-F1, List-F2, List-F3, List-G1, List-G2, List-G3, TABLE 4, TABLE 5, TABLE 6, TABLE 7, TABLE 8, TABLE 9, TABLE S1, TABLE S3, TABLE S4, TABLE S5, TABLE S6, TABLE S7, or a combination thereof;
- (ii) an miRNA selected from List-MR1, TABLE 2, TABLE 3, or a combination thereof;
- or
- (iii) a metabolite selected from List-ML1, or a combination thereof.
A method of selecting a therapeutic agent for treatment of dystonia in a subject, the method comprising
- a) measuring one or more dystonia biomarkers in the subject from a biological sample obtained from the subject, and
- b) selecting the therapeutic agent when the one or more dystonia biomarkers in the subject is
- i) aberrant compared to a reference level;
- or
- ii) not aberrant compared to a reference level,
- wherein the one or more dystonia biomarkers comprises
- (i) a protein selected from List-A1, List-A2, List-A3, List-A4, List-B1, List-B2, List-B3, List-C1, List-C2, List-C3, List-D1, List-D2, List-D3, List-E1, List-E2, List-E3, List-F1, List-F2, List-F3, List-G1, List-G2, List-G3, TABLE 4, TABLE 5, TABLE 6, TABLE 7, TABLE 8, TABLE 9, TABLE S1, TABLE S3, TABLE S4, TABLE S5, TABLE S6, TABLE S7, or a combination thereof;
- (ii) an miRNA selected from List-MR1, TABLE 2, TABLE 3, or a combination thereof;
- or
- (iii) a metabolite selected from List-ML1, or a combination thereof.
A method of predicting responsiveness to a treatment for dystonia, the method comprising
- a) obtaining a biosample from a subject having a dystonia;
- b) determining the expression level of one or more dystonia biomarkers in the biosample to create a proteomic profile;
- and
- c) comparing the subject's proteomic profile to a proteomic profile of a treatment-responsive subject;
- and
- i) predicting that the subject having a dystonia will be responsive to the treatment when the proteomic profiles are similar;
- or
- ii) predicting that the subject having a dystonia will not be responsive to the treatment when the proteomic profiles are aberrant,
- wherein the one or more dystonia biomarkers comprises
- (i) a protein selected from List-A1, List-A2, List-A3, List-A4, List-B1, List-B2, List-B3, List-C1, List-C2, List-C3, List-D1, List-D2, List-D3, List-E1, List-E2, List-E3, List-F1, List-F2, List-F3, List-G1, List-G2, List-G3, TABLE 4, TABLE 5, TABLE 6, TABLE 7, TABLE 8, TABLE 9, TABLE S1, TABLE S3, TABLE S4, TABLE S5, TABLE S6, TABLE S7, or a combination thereof;
- (ii) an miRNA selected from List-MR1, TABLE 2, TABLE 3, or a combination thereof;
- or
- (iii) a metabolite selected from List-ML1, or a combination thereof.
A method of classifying a subject having dystonia, the method comprising
- a) measuring one or more dystonia biomarkers in the subject from a biological sample obtained from the subject, and
- b) classifying the subject as
- i) having the one or more dystonia biomarkers when the one or more dystonia biomarkers in the subject is aberrant compared to a reference level, or
- ii) not having the one or more dystonia biomarker when the one or more dystonia biomarkers in the subject is not aberrant compared to a reference level,
- wherein the one or more dystonia biomarkers comprises
- (a) a protein selected from List-A1, List-A2, List-A3, List-A4, List-B1, List-B2, List-B3, List-C1, List-C2, List-C3, List-D1, List-D2, List-D3, List-E1, List-E2, List-E3, List-F1, List-F2, List-F3, List-G1, List-G2, List-G3, TABLE 4, TABLE 5, TABLE 6, TABLE 7, TABLE 8, TABLE 9, TABLE S1, TABLE S3, TABLE S4, TABLE S5, TABLE S6, TABLE S7, or a combination thereof;
- (b) an miRNA selected from List-MR1, TABLE 2, TABLE 3, or a combination thereof;
- or
- (c) a metabolite selected from List-ML1, or a combination thereof.
A method of identifying a dystonia biomarker in a subject, the method comprising:
- a) obtaining a biosample from a subject having a dystonia;
- b) obtaining a biosample from a subject not having a dystonia;
- c) determining the reference level of one or more proteins, miRNAs, and/or metabolites in the biosample from a subject having a dystonia;
- and
- d) identifying those proteins, miRNAs, and/or metabolites that are aberrant in the biosample obtained from the subject having a dystonia when compared to the biosample from the subject not having a dystonia;
- wherein those aberrant proteins, miRNAs, and/or metabolites are biomarkers of dystonia,
- optionally wherein the biosample comprises extracellular vesicles,
- further optionally wherein the method further comprises treating the subject having a dystonia, wherein treating the subject comprises administering one or more therapeutic agents, further optionally wherein the one or more therapeutic agents modulates the expression level of one or more aberrant dystonia biomarker.
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A pharmaceutical composition for treatment of a dystonia in a subject in need thereof, comprising one or more therapeutic agents as described herein and a pharmaceutically acceptable carrier, wherein the treatment comprises administering the pharmaceutical composition to the subject when one or more dystonia biomarkers in the subject is aberrant compared to a reference level.
Dependencies are inferred from the claim text.