Therapeutic agent for motor neuron disease

Abstract

An object of the present invention is to provide an agent effective for the treatment and/or prevention of motor neuron disease such as amyotrophic lateral sclerosis (ALS). The present invention provides a therapeutic and/or preventive agent for motor neuron disease comprising the following oligopeptide shown in any of (a) to (c) or a pharmaceutically acceptable salt thereof as an active ingredient: (a) an oligopeptide consisting of the amino acid sequence represented by Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1); (b) an oligopeptide consisting of an amino acid sequence having a deletion, substitution, insertion, or addition of one or several amino acids in Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1), and having an activity that inhibits neuronal cell death caused by a mutant superoxide dismutase-1 gene; and (c) a modified oligopeptide from the oligopeptide (a) or (b).

1 . A therapeutic and/or preventive agent for motor neuron disease comprising an oligopeptide shown in any of the following (a) to (c) or a pharmaceutically acceptable salt thereof as an active ingredient:
 (a) an oligopeptide consisting of the amino acid sequence represented by Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1);   (b) an oligopeptide consisting of an amino acid sequence having a deletion, substitution, insertion, or addition of one or several amino acids in Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1), and having an activity that inhibits neuronal cell death caused by a mutant superoxide dismutase-1 gene; and   (c) a modified oligopeptide from the oligopeptide (a) or (b).   
     
     
         2 . A therapeutic and/or preventive agent for motor neuron disease comprising DNA encoding the following oligopeptide (a) or (b) as an active ingredient:
 (a) an oligopeptide consisting of the amino acid sequence represented by Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1); and   (b) an oligopeptide consisting of an amino acid sequence having a deletion, substitution, insertion, or addition of one or several amino acids in Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1), and having an activity that inhibits neuronal cell death caused by a mutant superoxide dismutase-1 gene.   
     
     
         3 . The agent according to  claim 1  or  2 , wherein the motor neuron disease is amyotrophic lateral sclerosis (ALS). 
     
     
         4 . The agent according to  claim 1  or  2 , wherein the agent has the effect of delaying the onset of the motor neuron disease and ameliorating the motor function of a patient with the motor neuron disease. 
     
     
         5 . A fusion peptide of the following oligopeptide (a) or (b) with another peptide:
 (a) an oligopeptide consisting of the amino acid sequence represented by Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1); or   (b) an oligopeptide consisting of an amino acid sequence having a deletion, substitution, insertion, or addition of one or several amino acids in Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1), and having an activity that inhibits neuronal cell death caused by a mutant superoxide dismutase-1 gene.   
     
     
         6 . The fusion peptide according to  claim 5 , wherein another peptide is a signal peptide for extracellular secretion and/or a tag peptide for purification and detection. 
     
     
         7 . DNA encoding the following oligopeptide (a) or (b) or a fusion peptide according to  claim 5 :
 (a) an oligopeptide consisting of the amino acid sequence represented by Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1); or   (b) an oligopeptide consisting of an amino acid sequence having a deletion, substitution, insertion, or addition of one or several amino acids in Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1), and having an activity that inhibits neuronal cell death caused by a mutant superoxide dismutase-1 gene.   
     
     
         8 . A recombinant vector comprising DNA according to  claim 7 . 
     
     
         9 . A host cell transformed with DNA according to  claim 8 . 
     
     
         10 . A method for producing the following oligopeptide (a) or (b), characterized by culturing the host cell according to  claim 9  in a medium and collecting an oligopeptide expressed from the obtained culture:
 (a) an oligopeptide consisting of the amino acid sequence represented by Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1): and   (b) an oligopeptide consisting of an amino acid sequence having a deletion, substitution, insertion, or addition of one or several amino acids in Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO: 1), and having an activity that inhibits neuronal cell death caused by a mutant superoxide dismutase-1 gene.