Mirna based treatment monitoring in multiple sclerosis

Abstract

The present invention relates to methods of determining whether a patient responds to a therapeutic treatment of multiple sclerosis (MS), of monitoring the course of multiple sclerosis (MS) in a patient, of determining the risk for a relapse of multiple sclerosis (MS) in a patient, and of adjusting the dose of a therapeutic drug applied for therapeutic treatment of multiple sclerosis in a patient. Said methods are based on the determination of the level of at least one miRNA in a test sample isolated from the patient. The present invention also relates to a method of identifying a compound suitable for the treatment of multiple sclerosis in a patient. Further, the present invention relates to the use of a polynucleotide or a polynucleotide set for detecting a miRNA to determine whether a patient responds to a therapeutic treatment of multiple sclerosis, to monitor the course of multiple sclerosis in a patient, to determine the risk of a relapse of multiple sclerosis in a patient, to adjust the dose of a therapeutic drug applied for therapeutic treatment of multiple sclerosis in a patient, and to identify a compound suitable for the treatment of multiple sclerosis in a patient. Furthermore, the present invention relates to a kit for determining whether a patient responds to a therapeutic treatment of multiple sclerosis, for monitoring the course of multiple sclerosis in a patient, for determining the risk of a relapse of multiple sclerosis in a patient, for adjusting the dose of a therapeutic drug applied for therapeutic treatment of multiple sclerosis in a patient, or for identifying a compound suitable for the treatment of multiple sclerosis in a patient comprising means for determining the level of at least one miRNA in a test sample isolated from a patient.

1 .- 110 . (canceled) 
     
     
         111 . A method of determining whether a patient responds to a therapeutic treatment of Relapsing-Remitting Multiple Sclerosis (RRMS) comprising the step of:
 determining the level of at least one miRNA (present/comprised) in a blood cellular fraction obtained from a whole blood sample taken from a patient to whom at least once a drug to be used in said therapeutic treatment is administered, has been administered, or had been administered,   wherein the nucleotide sequence of the at least one miRNA is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 4.   
     
     
         112 . The method of  claim 111 , wherein the whole blood sample is taken from the patient after the first administration of said drug. 
     
     
         113 . The method of  claim 111 , wherein the level of the at least one miRNA is compared to a reference level of the at least one miRNA (present/comprised) in a blood cellular fraction obtained from a whole blood sample taken from the patient prior to the administration of the drug. 
     
     
         114 . The method of  claim 113 , wherein an increase of the level of the at least one miRNA when compared to the reference level of the at least one miRNA indicates that the patient responds to said treatment of RRMS. 
     
     
         115 . The method of  claim 111 , wherein the level of the at least one miRNA having a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2 is determined. 
     
     
         116 . The method of  claim 111 , wherein the patient is a human. 
     
     
         117 . The method of  claim 111 , wherein the drug is selected from the group consisting of natalizumab, interferon beta 1a, interferon beta 1 b, glatiramer acetate, alemtuzumab, fingolimod, dimethylfumarate, and mitoxantrone. 
     
     
         118 . A method of determining the risk for a relapse of Relapsing-Remitting Multiple Sclerosis (RRMS) in a patient comprising the step of:
 determining the level of at least one miRNA in a blood cellular fraction obtained from a whole blood taken from a patient which receives, has received, or had received a therapeutic treatment of RRMS,   wherein the nucleotide sequence of the at least one miRNA is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 4.   
     
     
         119 . The method of  claim 118 , wherein the whole blood sample is taken from the patient during or after therapeutic treatment of RRMS. 
     
     
         120 . The method of  claim 118 , wherein the level of the at least one miRNA is compared to a reference level of the at least one miRNA (present/comprised) in a blood cellular fraction obtained from a whole blood sample taken from the patient at an earlier point in time. 
     
     
         121 . The method of  claim 120 , wherein said earlier point in time lies within a period of therapeutic treatment of RRMS. 
     
     
         122 . The method of  claim 120 , wherein said reference level represents the maximal level of the at least one miRNA achievable in the patient by the therapeutic treatment of RRMS and wherein a decrease of the level of the at least one miRNA when compared to the reference level of the at least one miRNA indicates a risk of the patient for a relapse of RRMS. 
     
     
         123 . The method of  claim 118 , wherein the level of the at least one miRNA having a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2 is determined. 
     
     
         124 . The method of  claim 118 , wherein the patient is a human. 
     
     
         125 . The method of  claim 118 , wherein the therapeutic treatment involves the administration of a drug. 
     
     
         16 . The method of  claim 125 , wherein the drug is selected from the group consisting of natalizumab, interferon beta 1a, interferon beta 1b, glatiramer acetate, alemtuzumab, fingolimod, dimethylfumarate, and mitoxantrone.