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RU2018147040A - Способ лечения синдрома прадера-вилли - Google Patents

Способ лечения синдрома прадера-вилли Download PDF

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RU2018147040A
RU2018147040A RU2018147040A RU2018147040A RU2018147040A RU 2018147040 A RU2018147040 A RU 2018147040A RU 2018147040 A RU2018147040 A RU 2018147040A RU 2018147040 A RU2018147040 A RU 2018147040A RU 2018147040 A RU2018147040 A RU 2018147040A
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agonist
pde4i
receptor agonist
receptor
use according
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RU2018147040A
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RU2018147040A3 (ru
RU2748294C2 (ru
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Лиза Коул БЕРНЕТТ
Дитер ЭГЛИ
Рудольф Л. ЛЕЙБЕЛ
Сара КОТТЕР
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Зе Трастис Оф Коламбия Юниверсити Ин Зе Сити Оф Нью-Йорк
Лево Терапьютикс, Инк.
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Claims (15)

1. Применение ингибитора фосфодиэстеразы-4 (PDE4i) при лечении синдрома Прадера-Вилли (СПВ) у нуждающегося в этом субъекта, улучшая, устраняя или предотвращая, таким образом, один или несколько симптомов СПВ.
2. Применение по п. 1, в котором PDE4i повышает у субъекта концентрации или активность циклического аденозинмонофосфата (цАМФ).
3. Применение по п. 2, в котором СПВ характеризуется пониженной экспрессией Nhlh2.
4. Применение по п. 3, в котором пониженная экспрессия Nhlh2 приводит к пониженной экспрессии Pcsk1.
5. Применение по п. 2, в котором повышение концентраций или активности цАМФ повышает экспрессию Pcsk1.
6. Применение по п. 2, в котором PDE4i является селективным PDE4i.
7. Применение по п. 2, в котором PDE4i является неселективным PDE4L
8. Применение по п. 6, причем селективный PDE4i выбирают из группы, состоящей из AN2728, апремиласта, циломиласта, диазепама, ибудиласта, лютеолина, мезембренона, пикламиласта, рофлумиласта, ролипрама, Е6005, GSK356278 и МK0952.
9. Применение по п. 7, в котором неселективный PDE4i выбирают из метилированных ксантинов и их производных, кофеина, аминофиллина, 3-изобутил-1-метилксантина, параксантина, пентоксифиллина, теобромина и теофиллина.
10. Применение по п. 1, причем один или более симптомов включают в себя гиперфагию, пониженную интенсивность метаболизма, ожирение, гипогонадизм, сниженную выработку гормона роста, пониженный мышечный тонус, нарушения сна, нарушения со стороны желудочно-кишечного тракта, пониженную выносливость, пониженную способность к концентрации, ухудшение когнитивной деятельности, поведенческие нарушения, тревожное расстройство, задержку роста, пониженную способность превращения незрелых гормонов в зрелые и активные формы, а также диабет.
11. Применение по п. 1, причем один или несколько дополнительных терапевтических агентов, эффективных для лечения или улучшения одного или более симптомов СПВ, адаптируют для введения субъекту.
12. Применение по п. 10, в котором незрелые гормоны включают в себя один или более из инсулина, грелина, РГГР (рилизинг-гормон гормона роста), альфа-МСГ (эндогенный лиганд рецептора меланокортина 4), окситоцина, орексина, НФГМ, вазопрессина, нейропептида Y, АПБ (агути-подобный белок) и гонадотропина.
13. Применение по п. 11, в котором один или более дополнительных терапевтических агентов, эффективных для лечения или облечения СПВ, включают в себя инсулин, агонист рецептора инсулина, грелин, агонист рецептора грелина, РГГР, агонист рецептора РГГР, альфа-МСГ, агонист рецептора альфа-МСГ, окситоцин, агонист рецептора окситоцина, орексин, агонист рецептора орексина, НФГМ, агонист рецептора НФГМ, вазопрессин, агонист рецептора вазопрессина, нейропептид Y, агонист рецептора нейропептида Y, АПБ, агонист рецептора АПБ, гонадотропин, агонист рецептора гонадотропина или их комбинации.
14. Применение по п. 1, в котором PDE4i является МK0952.
15. Применение по п. 8, в котором PDE4i является МK0952.
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