Use of akt phosphorylation as a biomarker for prognosing neurodegenerative diseases and treating same

Abstract

The present invention relates to uses of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, analogues and derivatives thereof, for the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The present invention further provides a method for assessing responsiveness to treatment with the peptide of the invention. In addition, the present invention relates to prognosis of ALS progression, using Akt and phosphorylated Akt as biomarkers.

What is claimed is: 
     
         1 . A method for treating amyotrophic lateral sclerosis (ALS) in a subject in need thereof, comprising administering to a subject having a rapidly progressing ALS a therapeutically effective amount of an agent capable of activating a Akt pathway, thereby treating the ALS. 
     
     
         2 . The method according to  claim 1 , wherein said agent capable of activating said Akt pathway comprises a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2 and an analog or a derivative thereof. 
     
     
         3 . The method according to  claim 1 , wherein said agent capable of activating said Akt pathway is selected from the group consisting of a insulin-like growth factor 1 (IGF-I), vascular endothelial growth factor (VEGF), angiogenin, naphtho[1,2-b]furan-4,5-dione (NFD), ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), growth factor-beta (TGF-beta), glial-cell-line-derived neurotrophic factor (GDNF), Hepatic growth factor (HGF), fibroblast growth factor (FGF) and epidermal growth factor (EGF). 
     
     
         4 . A method for treating amyotrophic lateral sclerosis (ALS) in a subject in need thereof, comprising
 (a) assessing the level of pAkt and pAkt:tAkt ratio in bodily sample derived from the subject; and   (b) administering a therapeutically effective amount of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2 and an analog or a derivative thereof, to a subject having pAkt level or pAkt:tAkt ratio significantly below a control value.   
     
     
         5 . The method according to  claim 4 , wherein the bodily sample is derived from the peripheral blood, the lymph system or the muscle of the subject. 
     
     
         6 . The method according to  claim 5 , wherein said peripheral blood or said lymph system comprises lymphocytes. 
     
     
         7 . The method according to  claim 4 , wherein the control value corresponds to pAkt level or pAkt:tAkt ratio in a sample selected from the group consisting of: a bodily sample of a healthy individual, a bodily sample of an individual not afflicted with ALS, and a sample derived from a ALS subject having a slow disease. 
     
     
         8 . The method according to  claim 4 , wherein the peptide is comprised in a pharmaceutical composition in combination with at least one more therapeutic drug. 
     
     
         9 . The method according to  claim 8 , wherein the at least one more therapeutic drug is selected from the group consisting of: an oxidative agent, non-halogen activated-oxygen compounds, non-oxygen activated-halogen compounds, N-halo compounds and riluzole. 
     
     
         10 . The method according to  claim 8 , wherein the pharmaceutical composition further comprises a pharmaceutical acceptable excipient, carrier or diluent. 
     
     
         11 . The method according to  claim 4 , wherein treating comprises attenuating the progression of said ALS, alleviating symptoms of said ALS, delaying the appearance of ALS symptoms or improving management of said ALS. 
     
     
         12 . The method according to  claim 4 , wherein treating comprises administering the peptide by a route of administration selected from the group consisting of: oral, transdermal, parenteral, transmucosal, intrathecal, intracerebroventricular (ICV), intranasal, sublingual, intravenous and intraperitoneal. 
     
     
         13 . The method according to  claim 4 , wherein the peptide consists of an amino acid sequence selected from SEQ ID NO: 1, SEQ ID NO: 2 and an analog or a derivative thereof. 
     
     
         14 . A method for assessing responsiveness to treatment of a ALS with a peptide comprising an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2 or an analog or a derivative thereof, or a pharmaceutical composition comprising same, the method comprising:
 treating the subject with the peptide; and   assessing the level of pAkt or pAkt:tAkt ratio in bodily sample derived from a subject, wherein responsiveness to treatment is indicated by a pAkt level or pAkt:tAkt ratio significantly above a value of a pAkt level or pAkt:tAkt ratio in said subject prior to said treatment.   
     
     
         15 . The method according to  claim 14 , wherein the bodily sample is derived from the peripheral blood, the lymph system or a muscle of said subject. 
     
     
         16 . The method according to  claim 15 , wherein said peripheral blood or said lymph system comprises lymphocytes. 
     
     
         17 . The method according to  claim 14 , wherein the control value corresponds to pAkt level or pAkt:tAkt ratio in a sample selected from the group consisting of: a bodily sample of a healthy individual, a bodily sample of an individual not afflicted with any neurodegenerative disease and a sample derived from a ALS subject having a slow disease.