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1. Introduction
2. Worldwide prevalence of HCV infection
3. Natural history of HCV infection
4. Possible targets for anti-HCV therapy
5. Direct and indirect acting antivirals
6. Role of cyclophilins (Cyp)
7. Peptidy-prolyl cis-trans isomerase activity
8. Cyclophilins inhibitors (CypI)
9. CypI with confirmed anti-HCV activity
10. Alisporivir (Debio-025) vs. Cyclosporin A
11. Cyclophilin inhibitors - in vitro data
12. In vitro antiviral activity of CsA and alisporivir
13. Role of CypIs in HCV infection early studies
14. HCV non-structural proteins affected by CypI
15. Cyclophilins play a key role in HCV infection
16. CypI play a key role against HCV infection
17. Cyp play a key role in HCV infection
18. Cyclophilin A is a key player in HCV replication
19. Effect of CsA on HCV infection in chimpanzees
20. Early clinical data with Cyclosporin A (CsA)
21. CsA vs. tacrolimus for chronic HCV infection
22. HCV/HIV patients: anti-HCV effect of Debio025
23. Maximum HCV RNA and HIV RNA reductions
24. Alisporivir pharmacokinetics
25. Mean HCV RNA reduction during treatment (1)
26. Mean HCV RNA reduction during treatment (2)
27. Patients with undetectable HCV RNA at day 29
28. Adverse events during treatment
29. Effect of SOC medication in G1 & G4 patients
30. Effect of SOC medication in G2 & G3 patients
31. Long lasting virologic response
32. Mean HCV RNA during treatment with alisporivir
33. In vitro studies
34. An example of telaprevir monotherapy
35. Alisporivir remains active in replicon cell lines
36. Replicons containing resistant variants to VX950
37. Selection of alisporivir-resistant replicons
38. Replicons treated with direct acting antivirals
39. Identified mutations related to alisporivir
40. Reduction of sensitivity to alisporivir (1)
41. Reduction of sensitivity to alisporivir (2)
42. Conclusions
43. Thank you

Topics Covered

• HCV infection and its consequences
• Role of cyclophilins in HCV replication
• Anti-HCV effect of cyclophilin inhibitors
• Development of non-immunosuppressive cyclophilin inhibitors
• Clinical studies on possible use of cyclophilin inhibitors for hepatitis C treatment
• Efficacy and low risk of resistance

Links

Series:

• Antivirals

Categories:

• Biochemistry
• Clinical Practice
• Microbiology
• Pharmaceutical Sciences

Therapeutic Areas:

• Infectious Diseases

Talk Citation

Publication History

• Published on August 30, 2011

Financial Disclosures

• Prof. Robert Flisiak has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.