Treatment methods using polypeptides related to amyloid precursor protein

Abstract

The invention provides compounds having formulae comprising X 1 -Ser-Met-Arg-Glu-Arg-X 2 in which X 1 and X 2 are up to 30 amino acid residues and the formula represents a reverse-order sequence corresponding to amino acid residues 332 to 328 of human APP and from zero to 30 successive amino acid residues of human APP extending in each direction therefrom, The invention also provides the pentapeptide Ser-Met-Arg-Glu-Arg, corresponding to residues 332 to 328 of human amyloid precursor protein in reverse order, and the tripeptide Arg-Glu-Arg which corresponds residues 328 to 330 of human amyloid precursor protein, the tripeptide and pentapeptide being provided as pharmaceutical compositions. The invention further provides conjugates of the foregoing compounds which can cross the blood-brain barrier and pharmaceutical compositions containing such conjugates. The compounds and compositions of the invention are believed to be useful in the treatment of Alzheimer's disease and as cognitive enhancers and appropriate methods of medical treatment are disclosed.

1 . A method of treatment of a neurodegenerative disease in an animal, comprising:
 identifying an animal suffering or potentially suffering from a neurodegenerative disease; and   administering to the animal an amount of the compound Arg-Glu-Arg (SQ ID NO:9), wherein each amino acid residue is independently in the D-form or the L-form, or in the form of a salt thereof, effective to treat the neurodegenerative disease.   
     
     
         2 . A method of treatment of a neurodegenerative disease in an animal, comprising:
 identifying an animal suffering or potentially suffering from a neurodegenerative disease; and   administering to the animal an amount of a pharmaceutical composition comprising the compound Arg-Glu-Arg (SQ ID NO:9), wherein each amino acid residue is independently in the D-form or the L-form, or in the form of a salt thereof, and a pharmaceutically acceptable carrier, filler or excipient, said composition effective to treat the neurodegenerative disease.   
     
     
         3 . The method according to  claim 1  in which the animal is a human and the neurodegenerative disease is Alzheimer's disease. 
     
     
         4 . The method according to  claim 2  in which the animal is a human and the neurodegenerative disease is Alzheimer's disease. 
     
     
         5 . A method of producing a cognitive enhancement effect in an animal, comprising:
 providing an animal in which the effect is to be produced; and   administering to the animal an amount of the compound Arg-Glu-Arg (SEQ ID No:9), wherein each amino acid residue is independently in the D-form or the L-form, or in the form of a salt thereof, effective to produce the cognitive enhancement.   
     
     
         6 . A method of producing a cognitive enhancement effect in an animal comprising:
 providing an animal in which said effect is to be produced; and   administering to the animal an amount of a pharmaceutical composition comprising the compound Arg-Glu-Arg (SEQ ID No:9), wherein each amino acid residue is independently in the D-form or the L-form, or in the form of a salt thereof, and a pharmaceutically acceptable carrier, filler or excipient, said composition effective to produce the cognitive enhancement in the animal.   
     
     
         7 . The method according to  claim 5  in which the animal is a human. 
     
     
         8 . The method according to  claim 6  in which the animal is a human.