RNA interference therapy in lung transplant patients infected with respiratory syncytial virus
| Autor: | Jeffrey Cehelsky, Mark W. Rolfe, John P. DeVincenzo, Sara Nochur, Gary Albert, Jens Gottlieb, Akshay Vaishnaw, Marie Budev, Atul Humar, Jared Gollob, Allan R. Glanville, Martin R. Zamora |
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| Rok vydání: | 2010 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Adolescent medicine.medical_treatment Bronchiolitis obliterans Respiratory Syncytial Virus Infections Critical Care and Intensive Care Medicine Antiviral Agents Young Adult Double-Blind Method Intensive care Internal medicine Administration Inhalation medicine Lung transplantation Humans RNA Small Interfering Bronchiolitis Obliterans Respiratory tract infections business.industry Reverse Transcriptase Polymerase Chain Reaction Respiratory disease Syndrome respiratory system medicine.disease Respiratory Function Tests medicine.anatomical_structure C-Reactive Protein Treatment Outcome Viral pneumonia Immunology Cytokines RNA Interference business Viral load Respiratory tract Follow-Up Studies Lung Transplantation |
| Zdroj: | American journal of respiratory and critical care medicine. 183(4) |
| ISSN: | 1535-4970 |
| Popis: | Lower respiratory tract infections due to respiratory syncytial virus (RSV) are associated with development of bronchiolitis obliterans syndrome in lung transplant (LTX) recipients. ALN-RSV01 is a small interfering RNA targeting RSV replication.To determine the safety and explore the efficacy of ALN-RSV01 in RSV infection.We performed a randomized, double-blind, placebo-controlled trial in LTX recipients with RSV respiratory tract infection. Patients were permitted to receive standard of care for RSV. Aerosolized ALN-RSV01 (0.6 mg/kg) or placebo was administered daily for 3 days. Viral load was determined by quantitative reverse transcriptase-polymerase chain reaction on serial nasal swabs. Patients completed symptom score cards twice daily. Lung function, including the incidence of new-onset or progressive bronchiolitis obliterans syndrome, was recorded at Day 90.We enrolled 24 patients (ALN-RSV01, n = 16; placebo, n = 8); randomization was stratified by ribavirin use. ALN-RSV01 was well tolerated, with no drug-related serious adverse events or post-inhalation perturbations in lung function. Interpretation of viral measures was confounded by baseline differences between the two groups in viral load and time from symptom onset to first dose. Mean daily symptom scores were lower in subjects receiving ALN-RSV01, and the mean cumulative daily total symptom score was significantly lower with ALN-RSV01 (114.7 ± 63.13 vs. 189.3 ± 99.59, P = 0.035). At Day 90, incidence of new or progressive bronchiolitis obliterans syndrome was significantly reduced in ALN-RSV01 recipients compared with placebo (6.3% vs. 50%, P = 0.027).ALN-RSV01 was safe and may have beneficial effects on long-term allograft function in LTX patients infected with RSV. Clinical trial registered with www.clinicaltrials.gov (NCT 00658086). |
| Databáze: | OpenAIRE |
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