BACKGROUND OF THE INVENTION

Ticagrelor (Brilinta®) has been in clinical use as an anti-clotting drug, but not for the treatment of cystic disease. Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney, with a prevalence at birth ranging from 1 per 500 to 1000 people worldwide. ADPKD is caused by mutations in the PKD1 (85%) or PKD2 (15%) genes, which encode for polycystin-1 or polycystin-2 proteins, respectively. The hallmark of ADPKD is the formation of cysts in both kidneys, which gradually grow in size. Over the decades, new cysts form resulting in a decline of kidney function. By the age 55 years, about 50% of the ADPKD patients develop end-stage renal disease (ESRD), which requires dialysis therapy or renal transplantation.

There is no specific therapy for ADPKD. Its management is limited to control of high blood pressure, and symptomatic treatment of complications. Currently three different approaches are being tested to slow down the progression of cyst growth, but each has its own significant side effects.

Therefore, finding a treatment that can be sustained long-term without significant side effects is needed. The disclosed methods provide a new treatment for kidney diseases associated with elevated AVP (such as ADPKD) with a drug that is known to be safe for long term use in patients.

SUMMARY OF THE INVENTION

Disclosed are methods for treating kidney diseases associated with elevated AVP (such as ADPKD) in a subject, comprising the step of administering to the subject a composition comprising a therapeutically effective amount of ticagrelor or a derivative thereof, thereby treating the kidney disease in the subject.

Disclosed are methods for treating autosomal dominant polycystic kidney disease (ADPKD) in a subject, comprising the step of administering to the subject a composition comprising a therapeutically effective amount of ticagrelor or a derivative thereof, thereby treating ADPKD, wherein treating ADPKD comprises reducing cyst number and/or size or decreasing or preventing the increase in kidney size.

Disclosed are methods for treating ADPKD in a subject, comprising the step of administering to the subject a composition comprising a therapeutically effective amount of ticagrelor or a derivative thereof, thereby treating ADPKD, further comprising administering one or more additional therapeutics.

Disclosed are methods for treating a disease (such as ADPKD) associated with elevated AVP in a subject suffering therefrom, comprising the step of administering to the subject a composition comprising a therapeutically effective amount of ticagrelor or a derivative thereof, thereby treating the disease in the subject.

Disclosed are methods of decreasing arginine vasopressin (AVP) production in a subject comprising the step of administering to the subject a composition comprising an effective amount of ticagrelor, thereby decreasing AVP production.

Disclosed are methods for treating dilutional hyponatremia in a subject comprising the step of administering to the subject a composition comprising an effective amount of ticagrelor, thereby decreasing AVP production.

Disclosed are methods for treating ADPKD in a subject suffering therefrom, comprising the step of administering to the subject a composition comprising a therapeutically effective amount of ticagrelor or a derivative thereof, thereby treating ADPKD in the subject.

Disclosed are methods for inhibiting arginine vasopressin (AVP) production in hypothalamus comprising administering to hypothalamic cells or contacting hypothalamic cells with an effective amount of ticagrelor or a derivative thereof, thereby inhibiting arginine vasopressin (AVP) production in hypothalamic cells.

Disclosed are methods for inhibiting arginine vasopressin (AVP) production in a subject in need thereof, comprising administering to the subject a composition comprising an effective amount of ticagrelor or a derivative thereof, thereby decreasing AVP production in the subject.

Disclosed are methods for inhibiting cyst growth in a kidney of a subject suffering from a kidney disease (such as ADPKD) associated with elevated AVP, comprising administering to the subject a composition comprising an effective amount of ticagrelor or a derivative thereof, thereby inhibiting cyst growth in a kidney of the subject.

Disclosed are methods for lowering circulating levels of AVP in a subject, comprising administering to the subject an effective amount of a composition comprising an effective amount of ticagrelor or a derivative thereof, thereby lowering circulating levels of AVP in the subject.

Additional advantages of the disclosed method and compositions will be set forth in part in the description which follows, and in part will be understood from the description, or may be learned by practice of the disclosed method and compositions. The advantages of the disclosed method and compositions will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.

