RNA Interference Therapy in Lung Transplant Patients Infected with Respiratory Syncytial Virus

Abstract

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).

Hybrid pulmonary surfactant-coated nanogels mediate efficient in vivo delivery of siRNA to murine alveolar macrophages

“…In different pre-clinical models, a successful delivery in the respiratory tract of siRNA in the absence of a nanocarrier has been documented [33][34][35]. Moreover, promising results were obtained upon inhalation of free siRNA in human clinical trials for the treatment of patients infected with respiratory syncytial virus [36]. However, recent publications have clearly demonstrated the benefit of nanocarriers for siRNA inhalation therapy [9,32,37].…”

The Prophylaxis and Treatment with Antiviral Agents of Respiratory Syncytial Virus Infections

“…This is surprising given the very limited replication of RSV in this model [70], but gave confidence to these investigators to take the potential therapy into the clinic. Direct delivery of siRNA into the lungs allows a very localized effect and limits systemic spread [67,71]. ALN-01 was first given by intranasal administration to healthy volunteers 2 days before and 3 days after inoculation with a clinical isolate of the virus.…”

“…Since ALN-01 was safe and well-tolerated in the study, it would be justified to use a control RNA to judge if the effect is due to a direct or indirect antiviral effect. Further studies of ALN-01 have been done in patients who have undergone lung transplants [71]. In this heroic study, 521 transplant recipients were screened over 1 year for RSV infection.…”

Treatment of Respiratory Syncytial Virus Infection: Past, Present and Future

“…Patients were treated once daily for two days before and three days after RSV inoculation with a nasal spray containing either ALN-RSV01 or placebo, resulting in an approximately 38% decrease in the number of infections detected by quantitative culture of patients that received the investigational agent as compared to patients receiving placebo. In a second randomized, placebo-controlled Phase IIb trial, the safety and efficacy of the product was evaluated in lung transplant patients with a confirmed RSV infection (Zamora et al, 2011 Table 3. Overview of the different companies/institutions currently active in the development of RSV therapeutics and the different approaches applied.…”

“…Interpretation of the viral load data was reported to be confounded by baseline differences between the two groups and by time from symptom onset to first dose (Zamora et al, 2011). However, mean daily symptom scores were lower in individuals that received ALN-RSV01, and the mean cumulative daily total symptom score over a time period of 14 days was significantly lower with ALN-RSV01 (114.7 ± 63.13 vs. 189.3 ± 99.59, P = 0.035).…”