Modulation of transthyretin expression

Abstract

Compounds, compositions and methods are provided for modulating the expression of transthyretin. The compositions comprise oligonucleotides, targeted to nucleic acid encoding transthyretin. Methods of using these compounds for modulation of transthyretin expression and for diagnosis and treatment of diseases and conditions associated with expression of transthyretin are provided.

1 .- 18 . (canceled) 
     
     
         19 . A combination comprising a modulator of transthyretin expression and an anti-inflammatory drug. 
     
     
         20 . The combination of  claim 19 , wherein the modulator of transthyretin expression is an antisense compound, an antisense oligonucleotide, or a ribozyme capable of hybridizing to at least a portion of SEQ ID NO: 4. 
     
     
         21 . The combination of  claim 20 , wherein the antisense compound is single-stranded. 
     
     
         22 . The combination of  claim 20 , wherein the antisense compound comprises a modified oligonucleotide 20 to 25 nucleobases in length having at least one modified sugar moiety. 
     
     
         23 . The combination of  claim 22 , wherein the modified oligonucleotide is at least 95% complementary to SEQ ID NO: 4. 
     
     
         24 . The combination of  claim 19 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         25 . The combination of  claim 20 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         26 . The combination of  claim 21 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         27 . The combination of  claim 22 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         28 . The combination of  claim 23 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         29 . A method comprising administering to a subject a modulator of transthyretin expression and an anti-inflammatory drug. 
     
     
         30 . The method of  claim 29 , wherein the modulator of transthyretin expression is an antisense compound, an antisense oligonucleotide, or a ribozyme capable of hybridizing to at least a portion of SEQ ID NO: 4. 
     
     
         31 . The method of  claim 30 , wherein the antisense compound is single-stranded. 
     
     
         32 . The method of  claim 30 , wherein the antisense compound comprises a modified oligonucleotide 20 to 25 nucleobases in length having at least one modified sugar moiety. 
     
     
         33 . The method of  claim 32 , wherein the modified oligonucleotide is at least 95% complementary to SEQ ID NO: 4. 
     
     
         34 . The method of  claim 29 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         35 . The method of  claim 30 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         36 . The method of  claim 31 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         37 . The combination of  claim 32 , wherein the anti-inflammatory drug is a corticosteroid. 
     
     
         38 . The combination of  claim 33 , wherein the anti-inflammatory drug is a corticosteroid.