Compositions and methods for treatment of pouchitis
View Patent ↗The present invention relates methods of treating pouchitis by administering a pharmaceutical formulation suitable for rectal use, such as an enema or suppository, comprising an antisense oligonucleotide targeted to ICAM-1 to an individual
1. A method of treating pouchitis in a human, comprising:
identifying a human having pouchitis; and
rectally administering to said human a pharmaceutical composition, wherein said pharmaceutical composition comprises an antisense oligonucleotide that specifically hybridizes to and inhibits the activity of a human ICAM-1 mRNA, wherein said antisense oligonucleotide comprises from 16 to 20 phosphorothioate linked nucleosides that are each independently selected from 2′-deoxynucleosides and nucleosides comprising a 2′-F modified sugar moiety or a 2′-O-methoxyethyl modified sugar moiety, wherein said rectally administering reduces an occurrence of one or more clinical symptoms selected from a group consisting of stool frequency, rectal bleeding, fecal urgency, abdominal cramps, and fever, and wherein said rectally administering reduces said pouchitis.
2. The method of claim 1 , wherein said pharmaceutical composition is an enema.
3. The method of claim 1 , wherein said pharmaceutical composition is a suppository.
4. The method of claim 1 , wherein said pharmaceutical composition further comprises a penetration enhancer.
5. The method of claim 4 , wherein said penetration enhancer is a surfactant, fatty acid, bile salt, chelating agent or non-chelating non-surfactant.
6. The method of claim 1 , wherein said antisense oligonucleotide comprises at least one nucleoside comprising a 2′-O-methoxyethyl modified sugar moiety.
7. The method of claim 1 , wherein said antisense oligonucleotide comprises at least one nucleoside comprising a 2′-F modified sugar moiety.
8. The method of claim 1 , wherein said antisense oligonucleo-tide is a chimeric oligonucleotide having a plurality of linked 2′-deoxynucleosides flanked on each side by at least one nucleoside having a modified sugar moiety.
9. The method of claim 8 , wherein said modified sugar moiety is a 2′-O-methoxyethyl modified sugar moiety.
10. The method of claim 1 , wherein said antisense oligonucleotide comprises at least one modified nucleobase.
11. The method of claim 10 , wherein said modified nucleobase is a 5-methylcytosine modified nucleobase.
12. The method of claim 1 , wherein said antisense oligonucleotide is in a salt form.
13. The method of claim 1 , wherein said rectally administering reduces the occurrence of one or more endoscopy symptoms selected from the group consisting of edema, mucus exudate, granularity, friability, loss of vascular pattern, and ulceration.
14. The method of claim 1 , wherein said pharmaceutical composition is an enema formulation comprising hydroxypropyl methylcellulose, and said pharmaceutical composition is administered once daily.
15. The method of claim 14 , wherein said enema formulation comprises 240 mg of said antisense oligonucleotide.
16. The method of claim 1 , wherein said rectal administration occurs daily for at least 3 weeks or occurs daily for at least 6 weeks.
17. The method of claim 1 , wherein said antisense oligonucleotide is a single-stranded modified antisense oligonucleotide.
18. The method of claim 1 , wherein said antisense oligonucleotide consists of 20 linked nucleosides.
19. The method of claim 1 , wherein said pharmaceutical composition is administered at least once every 6 weeks, at least once a month or at least once a week.
20. The method of claim 8 , wherein said modified sugar moiety is a 2′-F modified sugar moiety.