Inhibitors of the cd95 signaling pathway for treatment of mds

Abstract

The present invention relates to inhibitors of the CD95 signaling pathway for the use in the treatment of Myelodysplastic Syndrom (MDS) wherein the MDS is selected from the IPSS low risk MDS subgroup and/or the IPSS intermediate-1 (int-1) risk MDS subgroup as well as a method for the diagnosis of MDS.

1 . A method for treating myelodysplastic syndrome (MDS), comprising the step of administering an inhibitor of CD95 signalling pathway to a patient in need thereof, wherein the MDS is selected from the IPSS low-risk MDS subgroup and/or the IPSS intermediate-1 (int-1) risk MDS subgroup, and wherein the inhibitor binds to the CD95 receptor (CD95) and/or the CD95 ligand (CD95L). 
     
     
         2 . The method according to  claim 1 , wherein the inhibitor is a compound which improves the growth of erythroid progenitors. 
     
     
         3 . The method according to  claim 1 , wherein the inhibitor is an antibody. 
     
     
         4 . The method according to  claim 1 , wherein the inhibitor is an antibody or fragment thereof that binds CD95L. 
     
     
         5 . The method according to  claim 1 , wherein the inhibitor is a CD95 receptor molecule or a CD95 ligand-binding portion thereof and/or CD95-ligand inhibitor. 
     
     
         6 . The method according to  claim 1 , wherein the inhibitor is a fusion protein that binds to a CD95L. 
     
     
         7 . The method according to  claim 6 , wherein the fusion protein comprises an extracellular CD95 domain or a functional fragment thereof and a human Fc domain or a functional fragment thereof. 
     
     
         8 . The method according to  claim 7 , wherein the inhibitor is APG101 and/or a functional derivative thereof, wherein APG101 comprises the domains CD95R (amino acids 26-172) of SEQ ID NO: 1 and IgG1-Fc (amino acids 172-400) of SEQ ID NO: 1. 
     
     
         9 . The method according to  claim 1 , wherein the MDS population is characterized by increased apoptosis during erythropoiesis. 
     
     
         10 . The method according to  claim 1 , wherein the MDS population is characterized by a severe defect of erythropoiesis without an excess of blasts. 
     
     
         11 . The method according to  claim 1 , wherein the MDS population is characterized by being resistant to erythropoiesis stimulating agents and/or colony stimulating factors. 
     
     
         12 . The method according to  claim 1 , wherein the inhibitor of CD95 signalling pathway is provided as pharmaceutical composition comprising pharmaceutically acceptable carriers, diluents and/or adjuvants. 
     
     
         13 . The method according to  claim 1 , wherein the inhibitor of CD95 signalling pathway is provided as pharmaceutical composition comprising at least one further active ingredient such as an erythropoiesis stimulating agent and/or an apoptosis inhibiting agent. 
     
     
         14 . The method according to  claim 1 , wherein the inhibitor of CD95 signalling pathway is administered at a total amount of 50 to 400 mg/week. 
     
     
         15 . The method according to  claim 14 , wherein the inhibitor of CD95 signalling pathway is administered at a total amount of 100 to 200 mg/week.