Compounds for use in polycystic kidney disease
Polycystic kidney disease is a cystic genetic disorder of the kidneys. Recent identification of signaling cascades de-regulated in PKD has led to the initiation of several clinical trials, but an effective therapy is still lacking. A new therapeutic paradigm is capable of improving the proliferation rate and cystic kidney volume in PKD.
1. A method of treating autosomal dominant polycystic kidney disease (ADPKD) in a subject in need thereof, comprising administering an effective amount of a pharmaceutical composition comprising 2-deoxyglucose (2DG).
2. A method of treatment according to claim 1 , wherein said 2DG is administered at a dosage in the range 20-250 mg/kg.
3. A method of treatment according to claim 1 , wherein said 2DG is administered at a dosage in the range 30-200 mg/kg.
4. A method of treatment according to claim 1 , wherein said 2DG is administered at a dosage in the range 40-150 mg/kg.
5. A method of treatment according to claim 1 , wherein said 2DG is administered at a dosage in the range 45-100 mg/kg.
6. A method of treatment according to claim 1 , wherein said 2DG is administered at a dosage in the range 50-65 mg/kg.
7. A method of treatment according to claim 1 , wherein said 2DG is administered at a dosage of about 60 mg/kg.
8. The method of treatment according to claim 1 , wherein said pharmaceutical composition further comprises at least one extracellular signal-regulated kinases (ERK) inhibitor selected from 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059), 1,4-Diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (UO126) or combinations thereof.
9. The method of treatment according to claim 1 , wherein said pharmaceutical composition further comprises at least one Serine/threonine-protein kinase (B-raf) inhibitor selected from Vemurafenib (RG7204), (E)-2,3-Dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-IH-pyrazol-4-yl]-IH-inden-1-one oxime (GDC-0879), N-[3-[(5-chloro-1H-pyrrolo[2,3 b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1 propanesulfonamide (PLX-4720), Sorafenib or combinations thereof.
10. The method of treatment according to claim 1 , wherein said pharmaceutical composition further comprises at least one mTOR inhibitor selected from rapamycin, metformin, 5-aminoimidazole-4-6-carboxamide ribunocleoside (AICAR) or combinations thereof.
11. The method of treatment according to claim 1 , wherein said pharmaceutical composition further comprises at least one compound selected from the group comprising 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059), 1,4-Diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (UO126), Vemurafenib (RG7204), E)-2,3-Dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-IH-pyrazol-4-yl]-IH-inden-1-one oxime (GDC-0879), N-[3-[(5-chloro-1H-pyrrolo[2,3 b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1 propanesulfonamide (PLX-4720), Sorafenib, rapamycin, metformin, 5-aminoimidazole-4-6-carboxamide ribonucleoside (AICAR) or combinations thereof.