Inhibitors of the CD95 signaling pathway for treatment of MDS
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) in a patient, comprising the step of administering a fusion protein APG101 comprising an extracellular CD95R domain having the amino acid sequence 26-172 of SEQ ID NO: 1 and a human Fc domain having the amino acid sequence 172-400 of SEQ ID NO: 1 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 the fusion protein binds to CD95 ligand (CD95L) and inhibits CD95 signalling pathway.
2. The method according to claim 1 , wherein the MDS population is characterized by increased apoptosis during erythropoiesis.
3. The method according to claim 1 , wherein the MDS population is characterized by a severe defect of erythropoiesis without an excess of blasts.
4. The method according to claim 1 , wherein the MDS population is characterized by being resistant to erythropoiesis stimulating agents (ESA) and/or colony stimulating factors.
5. The method according to claim 1 , wherein the fusion protein is administered in a pharmaceutical composition comprising pharmaceutically acceptable carriers, diluents and/or adjuvants.
6. The method according to claim 1 , wherein the fusion protein is administered in a pharmaceutical composition comprising at least one further active ingredient of an erythropoiesis stimulating agent and/or an apoptosis inhibiting agent.
7. The method according to claim 1 , wherein the fusion protein is administered at a total amount of 50 to 400 mg/week.
8. The method according to claim 7 , wherein the fusion protein is administered at a total amount of 100 to 200 mg/week.