AL-2 neurotrophic factor

Abstract

The present invention provides nucleic acids encoding AL-2 protein, as well as AL-2 protein produced by recombinant DNA methods. Such AL-2 protein and nucleic acid are useful in preparing antibodies and antagonists and in diagnosing and treating various neuronal disorders and disorders or conditions associated with angiogenesis.

1 . A method for accelerating neovascularization of a wound, comprising applying to the wound an angiogenically effective amount of a pharmaceutical composition comprising an isolated polypeptide comprising the amino acid sequence of 
 (a) the mature human AL-2 amino acid sequence shown in  FIGS. 1A-1C  (SEQ ID NO: 2) or  FIG. 2A-2D  (SEQ ID NO: 4); or    (b) a soluble AL-2 derived from SEQ ID NO: 2 or SEQ ID NO: 4; or    (c) a mammalian homolog or a conservative amino acid substitution variant of (a) having at least 95% sequence identity with SEQ ID NO: 2 or SEQ ID NO: 4,    and a physiologically acceptable carrier.    
     
     
         2 . The method of  claim 1  wherein said wound is due to surgical incision, burn, traumatized tissue, skin graft, or ulcer.  
     
     
         3 . The method of  claim 1  wherein normal healing of said wound is retarded.  
     
     
         4 . The method of  claim 3  wherein the retardation is due to advanced age, diabetes, cancer, or treatment with an anti-inflammatory drug or an anticoagulant.  
     
     
         5 . The method of  claim 1  wherein said composition is a topical composition.  
     
     
         6 . The method of  claim 5  wherein said topical composition is in the form of an irrigant or salve.  
     
     
         7 . The method of  claim 1  wherein said composition is contained in a suture, graft, or dressing.  
     
     
         8 . The method of  claim 1  wherein said composition is a sustained release composition.  
     
     
         9 . The method of  claim 1  wherein a clustered soluble AL-2 of the formula (soluble AL-2) n  is applied to the wound, wherein n is 2 or greater.  
     
     
         10 . The method of  claim 1  wherein an immunoadhesin comprising a soluble AL-2 is applied to the wound.  
     
     
         11 . The method of  claim 1  wherein a compound of the formula (AL-2) n X is applied to the wound, wherein AL-2 is any of the polypeptides defined in parts (a)-(c) of  claim 1 , and n is 2 or greater, and X is an organic linker covalently binding each AL-2.