Methods of treating prader willi syndrome and conditions associated with low basal metabolic rate or hyperphagia using a katp channel opener

Abstract

This invention relates to treating Prader-Willi Syndrome (PWS) using a KATP channel opener. The channel opener may be coadministered with other therapies used to treat PWS, such as human growth hormone, a wakefulness promoting agent, or a psychiatric or mood stabilizing drug, thereby allowing the baseline dosages of these other therapies to be decreased or making these other therapies unnecessary. The invention also relates to treating PWS based on the PWS nutritional phase of a patient, to prevent the patient's PWS nutritional phase from progressing or shift the patient's PWS nutritional phase back to an earlier phase. The invention further relates to treating PWS, and conditions associated with low basal metabolic rate or hyperphagia, with the KATP channel opener based on a patient's blood ketone levels.

1 . A method for treating Prader-Willi Syndrome, comprising administering a K ATP  channel opener and a second therapeutic agent to a patient in need thereof, wherein the second therapeutic agent is selected from the group consisting of (a) a human growth hormone (GH), wherein the dose of human growth hormone is reduced in comparison to a baseline or adjusted GH dose; (b) a psychiatric or mood stabilizing drug, wherein the dose of the psychiatric or mood stabilizing drug is reduced in comparison to a baseline psychiatric or stabilizing drug dose; and (c) a wakefulness promoting agent, wherein the dose of the wakefulness promoting agent is reduced in comparison to a baseline wakefulness promoting agent dose. 
     
     
         2 . The method of  claim 1 , wherein the baseline or adjusted GH dose is reduced by at least 10, 20, 50, 80, 90, or 100%. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the baseline psychiatric medication dose is reduced by at least 10, 20, 50, 80, 90, or 100%. 
     
     
         5 . The method of  claim 4 , wherein the psychiatric or mood stabilizing drug is selected from the group consisting of a selective serotonin reuptake inhibitor (SSRI), a norepinephrine reuptake inhibitor (NRI), a noradrenergic and specific serotonergic antidepressant (NaSSA), a serotonin-norepinephrine reuptake inhibitor (SNRI), a serotonin antagonist and reuptake inhibitor (SARI), a norepinephrine-dopamine reuptake inhibitor, a selective serotonin reuptake enhancer, a norepinephrine-dopamine disinhibitor, a tricyclic antidepressant, a tetracyclic antidepressant, a monoamine oxidase inhibitor (MAOI), N-acetylcysteine, cysteamine, oxytocin, a mood stabilizer, an anticonvulsant, a metabotropic glutamate receptor modulator, a typical antipsychotic, and an atypical antipsychotic. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the baseline wakefulness promoting agent dose is reduced by at least 10, 20, 50, 80, 90, or 100%. 
     
     
         8 . The method of  claim 7 , wherein the wakefulness promoting agent is selected from the group consisting of a stimulant, an amphetamine, a norepinephrine reuptake inhibitor (NRI), a norepinephrine-dopamine reuptake inhibitor (NDRI), a tricyclic antidepressant, a serotonin-norepinephrine reuptake inhibitor (SNRI), an H3-receptor antagonist, an orexin agonist, sodium oxybate, caffeine, and a eugeroic. 
     
     
         9 .- 13 . (canceled) 
     
     
         14 . A method for treating a disease or condition selected from the group consisting of Prader-Willi Syndrome, a condition associated with low basal metabolic rate, and a condition associated with hyperphagia, comprising administering a KATP channel opener to a patient in need thereof, wherein the patient's blood ketone level is less than a target level selected from the group consisting of 3.0, 2.5, 2.0, 1.5, 1.0, 0.6, 0.5, 0.4, 0.3, 0.2, and 0.1 mmol/mL. 
     
     
         15 . The method of  claim 14 , further comprising the step of administering a subsequent dose of the KATP channel opener to the patient, wherein the subsequent dose is higher than the previous dose if the patient's blood ketone level is less than or equal to the target level after administration of the previous dose, and wherein the subsequent dose is equal to or less than the previous dose if the patient's blood ketone level is greater than or equal to the target level after administration of the previous dose. 
     
     
         16 . A method for treating an autistic symptom or behavior or an autism spectrum disorder (ASD) comprising administering a K ATP  channel opener to a patient with Prader-Willi Syndrome in need thereof. 
     
     
         17 . The method of  claim 16 , wherein the patient meets the criteria for an ASD, which is indicated by an elevated score on the Pervasive Developmental Disorder-Mental Retardation questionnaire, or by criteria on the Autism Diagnostic Observation Schedule or the Autism Diagnostic Interview (Revised). 
     
     
         18 . The method of  claim 16 , wherein the autistic symptom or behavior or ASD is selected from the group consisting of an impairment in social interaction, language or communication; restricted, repetitive, or stereotyped behavior; stereotypies; a pronounced repetitive or compulsive behavior; skin picking; a need to tell, ask, or say; hoarding; ordering, arranging; symmetry or exactness; ritualized eating; rereading and rewriting; fearful of losing things; repeated checking; touching, tapping and rubbing; excessive washing; rectal picking; repetition of routines; and pulling hair out. 
     
     
         19 . The method of  claim 16 , wherein the K ATP  channel opener is diazoxide. 
     
     
         20 . The method of  claim 19 , wherein the dose of the diazoxide is at least 0.1, 0.5, 1.0, 2.0, 3.0, 5.0, 10.0, or 20.0 mg per kg of the subject's body weight. 
     
     
         21 . The method of  claim 20 , wherein the diazoxide is administered once or twice per day. 
     
     
         22 . The method of  claim 19 , wherein the dose of the diazoxide is less than 0.1, 0.5, 1.0, 2.0, 3.0, 5.0, 10.0, or 20.0 mg per kg of the subject's body weight. 
     
     
         23 . The method of  claim 22 , wherein the diazoxide is administered once or twice per day.