Therapeutic enzyme formulations and uses thereof in celiac sprue and/or dermatitis herpetoformis
Pharmaceutical formulations of glutenase enzymes are provided. The enzymes find particular use in the treatment of a Celiac or dermatitis herpetiformis patient.
1. A formulation comprising:
a combination of a prolyl endopeptidase (PEP) and Hordeum vulgare cysteine endoprotease B in an amount effective to decrease toxic gluten oligopeptide levels in a foodstuff and a pharmaceutically acceptable excipient, wherein said prolyl endopeptidase has a Kcat/Km of at least 250 s −1 M −1 for cleaving (SEQ ID NO:11) PQPQLPYPQPQLP.
2. The formulation according to claim 1 , wherein said prolyl endopeptidase is Flavobacterium meningosepticum PEP, Myxococcus xanthus PEP, Sphingomonas capsulata PEP, or Penicillium citrinum PEP.
3. A combination of a prolyl endopeptidase (PEP) and Hordeum vulqare cysteine endoprotease B in an amount effective to decrease toxic gluten oligopeptide levels in a foodstuff and a pharmaceutically acceptable excipient, wherein said prolyl endopeptidase is Sphingomonas capsulata PEP.
4. The formulation according to claim 1 , wherein said formulation is suitable for oral administration.
5. The formulation according to claim 1 , wherein said formulation comprises an enteric coating.
6. The formulation of claim 1 , wherein the cysteine endoprotease B is recombinantly produced.
7. The formulation of claim 6 , wherein the cysteine endoprotease is produced in E. coli.
8. The formulation of claim 1 , wherein the cysteine endoprotease B is in a proenzyme form that is activated under acidic conditions.
9. The formulation of claim 1 , wherein the cysteine endoprotease B is purified by affinity chromatography.
10. The formulation of claim 1 , wherein the cysteine endoprotease B comprises a histidine tag.
11. The formulation according to claim 6 , wherein the cysteine proteinase B is lyophilized.
12. The formulation according to claim 1 , wherein the mixture of a prolyl endopeptidase and cysteine endoprotease B is formulated in a pharmacologic unit dose.
13. The combination of claim 3 , wherein the Sphingomonas capsulata PEP is recombinantly produced.
14. The formulation of claim 6 , wherein the Sphingomonas capsulata PEP is produced in E. coli.
15. The combination of claim 3 , wherein the Sphingomonas capsulata PEP is purified by affinity chromatography.
16. The combination of claim 15 , wherein the Sphingomonas capsulata PEP comprises a histidine tag.
17. The combination of claim 3 , wherein the Sphingomonas capsulata PEP has been lyophilized.