Compositions, formulations and methods of treating preeclampsia-type disorders of pregnancy

Abstract

This invention discloses a method of and composition for treating a PE-type disorder in a subject in need of such treatment comprising administering to the subject a pharmaceutical composition containing a therapeutically effective amount of a TTR polypeptide in admixture with a pharmaceutically acceptable vehicle.

1 . A method of treating a PE-type disorder in a subject in need of such treatment comprising administering to the subject a pharmaceutical composition containing a therapeutically effective amount of a TTR polypeptide in admixture with a pharmaceutically acceptable vehicle. 
     
     
         2 . The method according to  claim 1  wherein the preeclampsia-type disorder is preeclampsia. 
     
     
         3 . The method according to  claim 1  wherein the preeclampsia-type disorder is eclampsia. 
     
     
         4 . The method according to  claim 1  wherein the preeclampsia-type disorder is HELLP syndrome. 
     
     
         6 . The method according to  claim 1  wherein said TTR polypeptide comprises TTR. 
     
     
         7 . The method according to  claim 1  wherein said TTR polypeptide comprises H—PTGTGESKAPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKT SE-NH—CH 2 —CH 2 —S—CH 2 —COELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTAND-NH—CH 2 —CH 2 —S—CH 2 —CO—PRRYTIAALLSPYSYSTTAVVTNPKE-OH. 
     
     
         8 . The method according to  claim 1  wherein said TTR peptide comprises fragments that are stable and include synthetic or enzyme breakdown products that mimic or modulate TTR activity or stabilizes native TTR protein. 
     
     
         9 . The method according to  claim 1  wherein said therapeutically effective amount of TTR polypeptide is between about 50 and 500 micrograms per kilogram body weight. 
     
     
         10 . The method of  claim 1  wherein said therapeutically effective amount of TTR polypeptide is about 50-100 mg/kg. 
     
     
         11 . The method of  claim 10  wherein therapeutically effective amount of TTR polypeptide is about 25-50 mg/kg. 
     
     
         12 . The method of  claim 1  wherein said therapeutically effective amount of TTR polypeptide is administered over a 24 hour period. 
     
     
         13 . The method according to  claim 1  wherein said TTR polypeptide is co-administered with a non-steroidal anti-inflammatory (NSAID). 
     
     
         14 . The method according to  claim 13  wherein said TTR polypeptide is co-administered with said NSAID at a molar ratio of TTR polypeptide to NSAID of from about 10:1 to about 1:1. 
     
     
         15 . The method according to  claim 1  wherein said TTR polypeptide is a stabilized TTR complex. 
     
     
         16 . The method according to  claim 15  wherein said TTR-complex includes stable TTR complexes with NSAIDS, metal cations, small molecular weight compounds including aromatic, heterocyclic, phenolics, arylheterocyclic and their derivatives, amino acids. 
     
     
         17 . The method according to  claim 13  wherein the non-steroidal anti-inflammatory composition is selected from the group consisting of diclofenac, flufenamic acid, diflunisal and aspirin. 
     
     
         18 . The method of  claim 13  wherein said co-administered amount of a TTR polypeptide and NSAID comprises from about 5 to about 100 mg/kg/day. 
     
     
         19 . The method of  claim 1  further comprising the step of monitoring the level of serum transthyretin in said subject subsequent to said administration. 
     
     
         20 . The method according to  claim 1  wherein the disorder is a hypertensive disorder. 
     
     
         21 . The method according to  claim 1  wherein the disorder is a kidney pathology, glomerular endotheliosis and excess excretion of protein or proteinuric disorders. 
     
     
         22 . The method according to  claim 1  further comprising reducing production of soluble anti-angiogenic factor. 
     
     
         23 . The method according to  claim 1  wherein the disorder is of placental origin. 
     
     
         24 . The method according to  claim 1  wherein said treatment induces pro-angiogenesis. 
     
     
         25 . The method according to  claim 1  wherein said need of said subject intrauterine growth restriction. 
     
     
         26 . A therapeutic composition comprising a therapeutically effective amount of a TTR polypeptide in a pharmaceutically acceptable vehicle. 
     
     
         27 . The composition according to  claim 26  in the form of a pyrogen-free, parenterally acceptable solution for systemic administration. 
     
     
         28 . The composition according to  claim 26  wherein the therapeutically effective amount of a TTR polypeptide is about 3.5 to about 500 mg. 
     
     
         29 . The said composition according to  claim 26  wherein said TTR polypeptide is selected from the group consisting of recombinant TTR, mutants of TTR, synthetic TTR, pharmaceutically active fragments of TTR and TTR-complexes.