Abstract: The present invention provides methods for the treatment of non-alcoholic steatohepatitis (NASH) including advanced fibrotic and/or cirrhotic stages of NASH. The methods include administration of a compound comprising a double stranded RNAi (dsRNAi) oligonucleotide, or a pharmaceutically acceptable salt thereof, to the patient. The dsRNAi oligonucleotide optionally contains an antisense strand and a sense strand, wherein the antisense strand and the sense strand form a duplex region, and wherein the antisense strand comprises a region of complementarity to a KHK mRNA target sequence.

Abstract: dsRNAi oligonucleotides can be used in methods for the treatment of NASH, preferably the advanced fibrotic and/or cirrhotic stages thereof, using dosage regimens comprising a loading phase followed by a maintenance phase.

Abstract: A method for identifying a protease secretion deficient strain of a microorganism involves producing a mutant of the microorganism, followed by adding the mutant to gel-filled wells of a microtitration plate, incubating the mutant in the gel-filled wells under conditions call sing the mutant to secrete proteins, separating the mutant from the gel, and measuring activity of a secretion protease of the microorganism in the gel, wherein either (i) the gel is a substrate for the secretion protease or (ii) the gel contains a substrate for the secretion protease.

Abstract: A method for identifying a protease secretion deficient strain of a microorganism involves producing a mutant of the microorganism, followed by adding the mutant to gel-filled wells of a microtitration plate, incubating the mutant in the gel-filled wells under conditions call sing the mutant to secrete proteins, separating the mutant from the gel, and measuring activity of a secretion protease of the microorganism in the gel, wherein either (i) the gel is a substrate for the secretion protease or (ii) the gel contains a substrate for the secretion protease.

Abstract: The invention relates to a method for identifying a protease secretion deficient strain of a microorganism, wherein: a mutant of the ciliate is added to a gel; and is incubated under conditions under which the mutant of the ciliate secretes proteins; said mutant of the ciliate is separated from the gel; wherein at least one substrate for at least one secretion protease of the ciliate is contained in said gel and/or said gel itself is the substrate and/or the substrate is added later and will at least in part diffuse into the gel; and the protease activity that has acted on the substrate is measured.