Targeting intracellular signaling as an antiviral strategy: aerosolized LASAG for the treatment of influenza in hospitalized patients
| Autor: | Tobias Welte, Gerhard Scheuch, Rolf Naumann, Karlheinz Nocker, Oliver Planz, Stephan Pleschka, Thomas Hofmann, Stephan Ludwig, Sebastian Canisius |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Patients Epidemiology Immunology Population Glycine medicine.disease_cause Placebo Antiviral Agents Microbiology Article Virus law.invention Mice 03 medical and health sciences Influenza A Virus H1N1 Subtype Randomized controlled trial law Virology Internal medicine Influenza Human Drug Discovery Clinical endpoint medicine Influenza A virus Animals Humans education education.field_of_study Aspirin business.industry Lysine Standard treatment General Medicine Middle Aged Hospitalization Mice Inbred C57BL Clinical trial Drug Combinations 030104 developmental biology Infectious Diseases Female Parasitology business |
| Zdroj: | Emerging Microbes & Infections |
| ISSN: | 2222-1751 |
| DOI: | 10.1038/s41426-018-0023-3 |
| Popis: | Influenza has been a long-running health problem and novel antiviral drugs are urgently needed. In pre-clinical studies, we demonstrated broad antiviral activity of D, L-lysine-acetylsalicylate glycine (LASAG) against influenza virus (IV) in cell culture and protection against lethal challenge in mice. LASAG is a compound with a new antiviral mode of action. It inhibits the NF-κB signal transduction module that is essential for IV replication. Our goal was to determine whether aerosolized LASAG would also show a therapeutic benefit in hospitalized patients suffering from severe influenza. The primary endpoint was time to alleviation of clinical influenza symptoms. The primary analysis was based on the modified intention-to-treat (MITT) population. This included all patients with confirmed influenza virus infection who received at least one treatment. The per protocol (PP) analysis set included all subjects from the MITT population who underwent at least 13 inhalations. In the MITT group, 48 (41.7%) participants (29 LASAG; 19 placebo) had severe influenza. The mean time to symptom alleviation was 56.2 h in the placebo group and 43.0 h in the LASAG group. The PP set consisted of 41 patients (24 LASAG; 17 placebo). The mean time to symptom alleviation in the LASAG group (38.3 h; P = 0.0365) was lower than that in the placebo group (56.2 h). In conclusion, LASAG improved the time to alleviation of influenza symptoms in hospitalized patients. The present phase II proof-of-concept (PoC) study demonstrates that targeting an intra-cellular signaling pathway using aerosolized LASAG improves the time to symptom alleviation compared to standard treatment. |
| Databáze: | OpenAIRE |
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