Secretagogues derived from oxalobacter formigenes

Abstract

The present invention relates to a secretagogue compound derived from oxalate degrading bacteria, for use in the treatment of an oxalate related disease and/or oxalate related imbalance in a subject, wherein the administration of the secretagogue results in a reduction of urinary oxalate and/or plasma oxalate in the subject. The invention further relates to a pharmaceutical composition comprising such a secretagogue compound, a method for treating a subject suffering from an oxalate related disease, and to a method for preparing a secretagogue.

1 - 13 . (canceled) 
     
     
         14 . A pharmaceutical product comprising:
 (i) an isolated secretagogue derived from  Oxalobacter formigenes , and   (ii) oxalate-degrading  Oxalobacter formigenes  bacteria.   
     
     
         15 . A pharmaceutical product according to  claim 14 , wherein the isolated secretagogue and the oxalate-degrading  Oxalobacter formigenes  bacteria are provided in separate compositions. 
     
     
         16 . The pharmaceutical product according to  claim 14 , further comprising one or more selected from oxalate-degrading enzymes, enzymes involved in oxalate metabolism, cofactors selected from vitamin B 6 , NAD + , NADP + , FAD, CoA, ATP and ADP, substrates selected from oxalate, glyoxylate, and 4-hydroxy-2-oxoglutarate, and combinations of any thereof. 
     
     
         17 . The pharmaceutical product according to  claim 14 , wherein the isolated secretagogue is selected from recombinantly expressed secretagogues and secretagogues extracted from conditioned media. 
     
     
         18 . The pharmaceutical product of  claim 14 , wherein the compositions are formulated for a route of administration selected from enteral, parenteral and topical route. 
     
     
         19 . The pharmaceutical product according to  claim 14 , wherein the amino acid sequence of the isolated secretagogue has at least 85% sequence identity to an amino acid sequence selected from SEQ ID NOs: 1-19. 
     
     
         20 . The pharmaceutical product according to  claim 14 , wherein the amino acid sequence of the isolated secretagogue has at least 85% sequence identity to an amino acid sequence selected from SEQ ID NOs: 3, 4, 6, 13 and 19. 
     
     
         21 . A method for reducing oxalate in a subject in need thereof, comprising administering to said subject (i) an isolated secretagogue derived from  Oxalobacter formigenes , and (ii) oxalate-degrading  Oxalobacter formigenes  bacteria, wherein the method is effective to reduce urinary and/or plasma oxalate in the subject. 
     
     
         22 . A method according to  claim 21 , wherein the isolated secretagogue and the oxalate-degrading  Oxalobacter formigenes  bacteria are administered from separate compositions. 
     
     
         23 . A method according to  claim 21 , wherein the compositions are formulated for a route of administration selected from enteral, parenteral and topical route. 
     
     
         24 . A method according to  claim 21 , further comprising administering to said subject one or more selected from oxalate-degrading enzymes, enzymes involved in oxalate metabolism, cofactors selected from vitamin B 6 , NAD + , NADP + , FAD, CoA, ATP and ADP, substrates selected from oxalate, glyoxylate, and 4-hydroxy-2-oxoglutarate, and combinations of any thereof. 
     
     
         25 . A method according to  claim 21 , wherein the amino acid sequence of the isolated secretagogue has at least 85% sequence identity to an amino acid sequence selected from SEQ ID NOs: 1-19. 
     
     
         26 . A method according to  claim 21 , wherein the amino acid sequence of the isolated secretagogue has at least 85% sequence identity to an amino acid sequence selected from SEQ ID NOs: 3, 4, 6, 13 and 19. 
     
     
         27 . A method according to  claim 21 , wherein the subject is suffering from an oxalate related disease and/or an oxalate related imbalance. 
     
     
         28 . A method according to  claim 27 , wherein the oxalate related disease is selected from primary hyperoxaluria, hyperoxaluria, absorptive hyperoxaluria, enteric hyperoxaluria, idiopathic calcium oxalate kidney stone disease (urolithiasis), vulvodynia, oxalosis associated with end-stage renal disease, cardiac conductance disorders, inflammatory bowel disease, Crohn's disease, ulcerative colitis, and disorders and conditions caused by or associated with gastrointestinal surgery, bariatric surgery, and/or antibiotic treatment.