Medicament for lct poisoning
AssigneeJohannes Gutenberg-Universitaet Mainz
InventorsChristoph VON EICHEL-STREIBER, Jessica REINEKE, Stefan TENZER, Hansjörg SCHILD, Maja RUPNIK
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Abstract
The medicament for the prevention or the relief of poisoning by large clostridial cytotoxins (LCTs), in particular Clostridium difficile toxins A and B (TcdA and TcdB), is characterized by containing as active ingredient at least one effector, namely an inhibitor or activator of the autocatalytic protease activity of LCTs (large clostridial cytotoxins).
Claims25
Method for preventing or relieving poisoning by LCT (=large clostridial cytotoxins), comprising:
- administering to a host in need thereof at least one inhibitor or activator of an autocatalytic protease activity of said LCT in an amount effective to prevent or relieve poisoning by LCT by stopping a cytotoxically effective fragment of said LCT which has glycosyl transferase function to arrive in a host's cell cytosol.
Method for preventing or relieving poisoning by LCTcomprising:
- administering a medicament that
- (1.) is suited for administration as a vaccine and
- (2.) as an antigen active ingredient
- (a) contains a TcdB protein fragment which comprises at least a DXG motif at position 1665, preferably an amino acid sequence of amino acid positions AS 1653 to AS 1678 [SEQ ID NO 1],
- and/or (b) contains a TcdA protein fragment which comprises at least a DXG motif at position 1662, preferably an amino acid sequence of amino acid positions
- AS 1651 to AS 1675 [SEQ ID NO:
- 2],
- and/or (c) contains a TcsL protein fragment which comprises at least a DXG motif at position 1666, preferably an amino acid sequence of amino acid positions AS 1654 to AS 1679 [SEQ ID NO:
- 3],
- and/or (d) contains a Tcnα protein fragment which comprises at least an amino acid sequence of AS 1641 to AS 1665 [SEQ ID NO:
- 4].
Method for stopping protease cleavage of a LCT, comprising providing an inhibitor of the autocataytic protease activity of one or more of the following proteases:
- protease of Clostridium difficile toxin A (TcdA);
- protease of Clostridium difficile toxin B (TcdB);
- protease of Clostridium sordellii lethal toxin (TcsL) or protease of Clostridium novyi α-toxin (Tcnα), wherein the inhibitor interacts with the protease of Clostridium difficile toxin A (TcdA);
- Clostridium difficile toxin B (TcdB);
- Clostridium sordellii lethal toxin (TcsL) or Clostridium novyi α-toxin (Tcnα) respectively, and inhibits said protease activity to autocatalytically split off the cytotoxically effective fragment of said Clostridium difficile toxin A (TcdA);
- Clostridium difficile toxin B (TcdB);
- Clostridium sordellii lethal toxin (TcsL) or Clostridium novyi α-toxin (Tcnα), respectively, outside a host cell.
Dependencies are inferred from the claim text.