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 .- 15 . (canceled) 
     
     
         16 . A method of treating autistic symptoms or behaviors associated with Prader-Willi Syndrome (PWS) in a patient in need thereof, comprising administering a K ATP  channel opener or a salt thereof to the patient for at least 2 weeks, 3 weeks, or 56 weeks. 
     
     
         17 . The method of  claim 16 , wherein the K ATP  channel opener is diazoxide or a salt thereof. 
     
     
         18 . The method of  claim 16 , further comprising administering a second therapeutic agent to the patient. 
     
     
         19 . The method of  claim 18 , wherein the second therapeutic agent is a psychiatric or mood stabilizing drug, or a wakefulness promoting agent. 
     
     
         20 . The method of  claim 19 , wherein the second therapeutic agent is a psychiatric or mood stabilizing drug selected from the group consisting of: a selective serotonin reuptake inhibitor (SSRI), norepinephrine reuptake inhibitor (NRI), noradrenergic and specific serotonergic antidepressant (NaSSA), serotonin-norepinephrine reuptake inhibitor (SNRI), serotonin antagonist and reuptake inhibitor (SARI), norepinephrine-dopamine reuptake inhibitor, selective serotonin reuptake enhancer, norepinephrine-dopamine disinhibitor, tricyclic antidepressant, tetracyclic antidepressant, monoamine oxidase inhibitor (MAOI), N-acetylcysteine, cysteamine, oxytocin, mood stabilizer, anticonvulsant, metabotropic glutamate receptor modulator, typical antipsychotic, and an atypical antipsychotic. 
     
     
         21 . The method of  claim 19 , wherein the second therapeutic agent is a wakefulness promoting agent selected from the group consisting of: a stimulant, an amphetamine, a norepinephrine reuptake inhibitor (NRI), norepinephrine-dopamine reuptake inhibitor (NDRI), a tricyclic antidepressant, a serotonin-norepinephrine reuptake inhibitor (SNRI), an H 3 -receptor antagonist, an orexin agonist, sodium oxybate, caffeine, and a eugeroic. 
     
     
         22 . The method of  claim 16 , wherein the patient has an elevated score on the Pervasive Developmental Disorder-Mental Retardation questionnaire that is indicative of an ASD, or meets the criteria for an ASD on the Autism Diagnostic Observation Schedule or the Autism Diagnostic Interview, Revised. 
     
     
         23 . The method of  claim 16 , wherein the autistic symptom or behavior 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. 
     
     
         24 . A method of reducing obesity, treating diabetes, inhibiting fasting insulin secretion, inhibiting stimulated insulin secretion, elevating energy expenditure, elevating beta oxidation of fat, or inhibiting hyperphagia in a patient having PWS in need thereof, comprising administering a K ATP  channel opener or a salt thereof to the patient for at least 2 weeks, 3 weeks, or 56 weeks. 
     
     
         25 . The method of  claim 24 , wherein the K ATP  channel opener is administered to cause one or more of the following improvements in the patient: normalized IGF- 1  levels;
 improved lean body mass; decreased body fat; modulated bone mineral density; normalized adult height; improved cognition, tone, endurance, stamina, strength, agility, or motor development; positively-affected nitrogen balance; and, increased energy expenditure.   
     
     
         26 . The method of  claim 24 , further comprising administering a second therapeutic agent to the patient. 
     
     
         27 . The method of  claim 26 , wherein the second therapeutic agent is human growth hormone. 
     
     
         28 . The method of  claim 24 , wherein the PWS nutritional phase of the patient is selected from the group consisting of Phase o, 1a, 1b, 2a, 2b, 3, and 4, and the K ATP  channel opener is administered to shift the patient's PWS nutritional phase back to an earlier phase. 
     
     
         29 . The method of  claim 24 , wherein the K ATP  channel opener is diazoxide or a salt thereof. 
     
     
         30 . A method of treating PWS, a condition associated with low basal metabolic rate, or a condition associated with hyperphagia in a patient in need thereof, comprising administering an increased dose of a K ATP  channel opener to the patient if the patient's blood ketone level is less than or equal to a target level, the target level selected from the group consiting 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/L, and wherein the increased dose of the K ATP  channel opener is increased until the patient's blood ketone level is at the target level. 
     
     
         31 . The method of  claim 30 , wherein the K ATP  channel opener is diazoxide or a salt thereof.