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 reducing one or more aggressive behaviors in a subject having Prader-Willi syndrome (PWS) or Smith-Magenis syndrome (SMS), the method comprising administering to said subject for at least 10 weeks a pharmaceutical formulation comprising an effective amount of diazoxide or a pharmaceutically acceptable salt thereof, wherein administration reduces one or more aggressive behaviors in the subject.
2. The method of claim 1 wherein the pharmaceutically acceptable salt is diazoxide choline.
3. The method of claim 1 wherein said pharmaceutical formulation is administered orally.
4. The method of claim 1 wherein the pharmaceutical formulation includes at least one excipient which affects the rate of release of diazoxide or a pharmaceutically acceptable salt thereof.
5. The method of claim 4 wherein the pharmaceutical formulation includes at least one excipient that delays release of diazoxide or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 wherein the pharmaceutical formulation further comprises at least one other active ingredient.
7. The method of claim 1 further comprising administering human growth hormone to the subject.
8. The method of claim 7 wherein said human growth hormone is administered by injection.
9. The method of claim 1 wherein said administering is carried out for one or more years.
10. The method of claim 1 , wherein the circulating concentration of IGF-1 is not increased.
11. The method of claim 1 in which a second therapeutic product is administered, wherein the second product is intended to further reduce the one or more aggressive behaviors.
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. A method of reducing one or more aggressive behaviors in a subject having Prader-Willi syndrome (PWS) or Smith-Magenis syndrome (SMS), the method comprising administering to said subject for at least 10 weeks an effective amount of a formulation consisting essentially of diazoxide or a pharmaceutically acceptable salt thereof, wherein administration reduces one or more aggressive behaviors in the subject.