Uses
Alicaforsen can be used as Anti-inflammatory used in the treatment of steroid dependent Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis, and renal transplant (anti-ICAM-1 antisens）.
Biological Functions
Alicaforsen is a phosphorothioate oligodeoxynucleotide 20 bases in length with a sequence complementary to the 3 -untranslated region of the mRNA of human ICAM-1. Hybridization of ISIS 2302 to mRNA inhibits expression of the ICAM-1 protein in response to inflammatory stimuli. Initial tests of activity were performed in mice using a analogous antisense oligonucleotide that is active against the analogous mouse ICAM molecule. Studies with this oligonucleotide showed that it had anti-inflammatory activity in models of organ transplant rejection, ulcerative colitis, and collagen-induced arthritis.
Toxicities in the mouse model were similar to those observed with other antisense
oligonucleotides and were independent of the suppression of ICAM-1 expression.
Immune stimulation, kidney changes, liver abnormalities, and increased clotting times
were observed, but all toxicities were reversible and occurred at doses well above those
required for pharmacological activity. No genetic toxicity was observed.
