Nonselective metabotropic glutamate receptor activators for treatment of anorexia nervosa and binge eating disorder
AssigneeThe Children's Hospital of Philadelphia
InventorsHakon Hakonarson, Charlly Kao
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Abstract
This application relates to methods of diagnosing and treating anorexia nervosa (AN) and binge eating disorder (BED) with a nonselective activator of metabotropic glutamate receptors (mGluRs).
Claims111
A method of treating anorexia nervosa (AN) in a subject comprising administering a therapeutically effective amount of a nonselective metabotropic glutamate receptor (mGluR) activator to a subject having at least one genetic alteration in a mGluR network gene, thereby treating AN.
A method of treating binge eating disorder (BED) in a subject comprising administering a therapeutically effective amount of a nonselective metabotropic glutamate receptor (mGluR) activator to a subject having at least one genetic alteration in a mGluR network gene, thereby treating BED.
A method of treating anorexia nervosa (AN) and binge eating disorder (BED) in a subject comprising administering a therapeutically effective amount of a nonselective metabotropic glutamate receptor (mGluR) activator to a subject having at least one genetic alteration in a mGluR network gene, thereby treating AN and BED.
The method of any of the preceding claims, wherein the genetic alteration is a copy number variation (CNV).
The method of any one of the preceding claims, wherein the genetic alteration is in at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, or all Tier 1 mGluR network genes.
The method of any one of the preceding claims, wherein the genetic alteration is in at least 2, 3, 4, 5, 10, 20, 30, 50, 100, 150, 175, or all Tier 2 mGluR network genes.
The method of any one of the preceding claims, wherein the genetic alteration is in at least 2, 3, 4, 5, 10, 20, 50, 100, 200 300, 400, 500, or all Tier 3 mGluR network genes.
The method of any one of the preceding claims, wherein the genetic alteration is not in one or more of GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7 or GRM8.
The method of any one of the preceding claims, wherein the subject has a genetic alteration in at least two mGluR network genes.
The method of any one of the preceding claims, wherein the subject has the bingeing and/or purging subtype of AN.
The method of any one of the preceding claims, wherein the subject has the restricting subtype of AN.
The method of any one of the preceding claims, wherein the subject is a pediatric or adolescent subject, such as a subject between the ages of 5 and 17, 8 and 17, 5 and 12, 5 and 8, 8 and 12, 13 and 17, 13 and 18, or 12 and 17.
The method of any one of the preceding claims, wherein the subject is an adult.
The method of any one of the preceding claims, wherein the nonselective mGluR activator is fasoracetam.
The method of any one of the preceding claims, wherein the activator is administered in combination with non-pharmaceutical therapy, such as brain stimulation, for example vagus nerve stimulation, repetitive transcranial magnetic stimulation, magnetic seizure therapy, and/or deep brain stimulation.
The method of any one of the preceding claims, wherein the genetic alteration is detected by a process comprising administering a genetic test comprising obtaining a sample from the subject, optionally isolating nucleic acid from the sample, optionally amplifying the nucleic acid, and analyzing the nucleic acid for a genetic alteration in at least one mGluR network gene.
A method of treating binge eating disorder (BED) in a subject comprising administering a nonselective mGluR activator to the subject, thereby treating BED.
A method of treating anorexia nervosa (AN) in a subject comprising administering a nonselective mGluR activator to the subject, thereby treating AN.
A method of treating BED and AN in a subject comprising administering an a nonselective mGluR activator to the subject, thereby treating BED and AN.
The method of any one of claims 54-58, wherein the genetic test comprises analyzing the nucleic acid for a CNV or SNV in at least 2, 3, 4, 5, 10, 20, 50, 100, 200 300, 400, 500, or all Tier 3 mGluR network genes.
The method of any one of claims 54-60, wherein the genetic test does not assess CNVs or SNVs in one or more of GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7 or GRM8.
A method for diagnosing anorexia nervosa (AN) in a subject, the method comprising:
- a) obtaining a biological sample from the subject;
- b) assaying nucleic acid from the sample to determine whether a genetic alteration is present in one or more genes in the mGluR network;
- and
- c) diagnosing the subject with AN if a genetic alteration is present in one or more genes in the mGluR network.
A method for diagnosing binge eating disorder (BED) in a subject, the method comprising:
- a) obtaining a biological sample from the subject;
- b) assaying nucleic acid from the sample to determine whether a genetic alteration is present in one or more genes in the mGluR network;
- and
- c) diagnosing the subject with BED if a genetic alteration is present in one or more genes in the mGluR network.
The method of any one of the preceding claims, wherein the genetic alteration is in one or more genes in the mGluR network at the corresponding chromosomal regions listed in FIGS. 1 to 3.
A method for determining whether a subject is susceptible to developing anorexia nervosa (AN) and/or binge eating disorder (BED), the method comprising:
- a) obtaining a biological sample from the subject;
- b) assaying nucleic acid from the sample to determine whether a genetic alteration in one or more genes in the mGluR network is present in the nucleic acid;
- and
- c) determining that the subject is susceptible to developing AN and/or BED if a genetic alteration is present in one or more one or more genes in the mGluR network.
A system for detecting a genetic alteration related to anorexia nervosa (AN) or binge eating disorder in a subject, comprising probes specific for and capable of determining the presence of a genetic alteration in:
- i) at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, or all Tier 1 mGluR network genes;
- ii) at least 1, 2, 3, 4, 5, 10, 20, 30, 50, 100, 150, 175, or all Tier 2 mGluR network genes;
- and/or iii) at least 1, 2, 3, 4, 5, 10, 20, 50, 100, 200 300, 400, 500, or all Tier 3 mGluR network genes.
Dependencies are inferred from the claim text.