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 human growth hormone (GH) to a patient in need thereof, wherein the dose of human growth hormone is reduced in comparison to a baseline or adjusted GH 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 . A method for treating Prader-Willi Syndrome, comprising administering a K ATP  channel opener and a psychiatric or mood stabilizing drug to a patient in need thereof, wherein the dose of the psychiatric or mood stabilizing drug is reduced in comparison to a baseline psychiatric or stabilizing drug dose. 
     
     
         4 . The method of  claim 3 , wherein the baseline psychiatric medication dose is reduced by at least 10, 20, 50, 80, 90, or 100%. 
     
     
         5 . The method of  claim 3 , 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 . A method for treating Prader-Willi Syndrome, comprising administering a K ATP  channel opener and a wakefulness promoting agent to a patient in need thereof, wherein the dose of the wakefulness promoting agent is reduced in comparison to a baseline wakefulness promoting agent dose. 
     
     
         7 . The method of  claim 7 , 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 . A method for treating Prader-Willi Syndrome comprising administering a K ATP  channel opener to a patient in need thereof, wherein the patient is in a PWS nutritional phase selected from the group consisting of 0, 1a, 1b, 2a, 2b, 3, and 4. 
     
     
         10 . The method of  claim 10 , wherein the patient's PWS nutritional phase is prevented from progressing to a later phase. 
     
     
         11 . The method of  claim 11 , wherein the patient is in PWS nutritional phase 1a, 1b, 2a, or 2b and wherein the patient's PWS nutritional phase is prevented from progressing to phase 1b, 2a, 2b, or 3. 
     
     
         12 . The method of  claim 10 , wherein the patient's PWS nutritional phase is shifted back to an earlier PWS nutritional phase. 
     
     
         13 . The method of  claim 13 , wherein the patient is in PWS nutritional phase 3 or 4, and wherein the patient's PWS nutritional phase is shifted back to phase 1a, 1b, 2a, or 2b. 
     
     
         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 K ATP  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 K ATP  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 autistic symptoms or behaviors associated with Prader-Willi Syndrome comprising administering a K ATP  channel opener to a patient in need thereof.