Therapy for cellular accumulation in chronic inflammatory diseases

Abstract

The present invention provides a novel method for the treatment of cellular accumulation in chronic inflammatory diseases such as rheumatoid arthritis. The method includes gene delivery and gene expression that is capable of enhancing apoptosis of accumulating cells and those cells which recruit accumulating cells. Also provided are diagnostic methods for detecting cellular accumulation diseases.

1 - 11 . (canceled)  
   
   
       12 . A method for reducing accumulation of synoviocytes in an inflamed joint in a mammal, comprising administering to said joint a composition comprising a nucleic acid with a sequence encoding a polypeptide that promotes apoptosis in the synoviocyte.  
   
   
       13 . The method of  claim 12 , whereby apoptosis is induced in synoviocytes present in a joint to which it is administered.  
   
   
       14 . The method of  claim 12 , wherein the nucleic acid is a viral vector.  
   
   
       15 . The method of  claim 14 , wherein the viral vector is an adenovirus or adeno-associated virus vector.  
   
   
       16 . The method of  claim 14 , wherein in the viral vector is replication deficient.  
   
   
       17 . The method of  claim 12 , wherein the composition is formulated such that the nucleic acid is present in microspheres, liposomes, or macromolecular complexes.  
   
   
       18 . The method of  claim 12 , wherein the polypeptide is selected from p53, p21Waf, ras, proteins in the Bax family, and proteins in the ICE family.  
   
   
       19 . The method of  claim 12 , wherein the polypeptide is a peptidomimetic or binding agent of p53, p21 Waf, ras, a protein in the Bax family, or a protein in the ICE family.  
   
   
       20 . The method of  claim 12 , wherein said mammal has rheumatoid arthritis.  
   
   
       21 . The method of  claim 12 , wherein the mammal has ankylosing spondylitis, psoriatic arthritis, or inflammatory bowel disease.  
   
   
       22 . A method for reducing accumulation of synoviocytes in an inflamed joint in a mammal, comprising restoring or enhancing the process of apoptosis in said synoviocyte.  
   
   
       23 . The method of  claim 22 , comprising contacting said synoviocytes with a nucleic acid expression vector that causes expression of a protein selected from the group consisting of p53, p21Waf, ras, proteins of the Bax family, and proteins of the ICE family, or a peptidomimetic or binding agent of any protein in said group.