Methods for treating subjects with prader-willi syndrome or smith-magenis syndrome
Provided are immediate or prolonged administration of certain potassium ATP (K ATP ) channel openers, optionally in combination with growth hormone, to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of K ATP channel openers that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are methods of co-administering K ATP channel openers with other drugs (e.g., in combination with growth hormone) to treat diseases of humans and animals (e.g., Prader-Willi Syndrome (PWS), Smith-Magenis syndrome (SMS), and the like.
1. A method of increasing by at least 2% the lean body mass or the lean body mass/fat mass ratio in a subject having Prader-Willi Syndrome (PWS) or Smith-Magenis syndrome (SMS), comprising administering to the subject for at least 10 weeks a pharmaceutical formulation comprising an effective amount of a K ATP channel opener or a pharmaceutically acceptable salt thereof, wherein said lean body mass or lean body mass/fat ratio in the subject is increased by at least 2% after 10 weeks of administration compared to lean body mass or lean body mass/fat ratio prior to the start of the administration, and
wherein the method does not comprise administering human growth hormone to the subject.
2. The method of claim 1 , wherein the lean body mass or the lean body mass/fat mass ratio of the subject is increased by at least 3% after at least 10 weeks of administering the pharmaceutical formulation.
3. The method of claim 1 , wherein the lean body mass or the lean body mass/fat mass ratio of said subject is increased by at least 4% after at least 10 weeks of administering the pharmaceutical formulation.
4. The method of claim 1 , wherein the lean body mass or the lean body mass/fat mass ratio of said subject is increased by at least 5% after at least 10 weeks of administering the pharmaceutical formulation.
5. The method of claim 1 , wherein the pharmaceutical formulation further comprises at least one other active ingredient.
6. The method of claim 1 , wherein the pharmaceutical formulation comprises at least one excipient that affects the rate of release of the K ATP channel opener or the pharmaceutically acceptable salt thereof.
7. The method of claim 1 , wherein the pharmaceutical formulation comprises at least one excipient that delays release of the K ATP channel opener or the pharmaceutically acceptable salt thereof.
8. The method of claim 1 , wherein hyperphagia of the subject is reduced by at least 10% after at least 10 weeks of administering the pharmaceutical formulation.
9. The method of claim 8 , wherein hyperphagia of the subject is reduced by at least 20% after at least 10 weeks of administering the pharmaceutical formulation.
10. The method of claim 9 , wherein hyperphagia of the subject is reduced by at least 30% after at least 10 weeks of administering the pharmaceutical formulation.
11. The method of claim 1 , wherein the subject's circulating concentration of IGF-1 is not increased after at least 10 weeks of administering the pharmaceutical formulation.
12. The method of claim 1 , wherein the pharmaceutical formulation is administered twice per day.
13. The method of claim 1 , wherein the pharmaceutical formulation is administered once per day.
14. The method of claim 1 , wherein the pharmaceutical formulation is administered for 1 or more years.
15. The method of claim 1 , wherein the K ATP channel opener is diazoxide, or the pharmaceutical formulation comprises a pharmaceutically acceptable salt of diazoxide.
16. The method of claim 15 , wherein the pharmaceutically acceptable salt is diazoxide choline.
17. The method of claim 15 , wherein the diazoxide or a pharmaceutically acceptable salt thereof is administered orally.
18. The method of claim 1 , wherein the subject is an adult.
19. The method of claim 1 , wherein the subject is over the age of 16.