Potential Application of Viral Empty Capsids for the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome
Abstract
Acute respiratory distress syndrome (ARDS) is a critical condition of lung malfunction that requires ventilation and other supportive treatment in intensive care units. There is no specific treatment for ARDS, which is associated with high morbidity, mortality, and financial cost. ARDS is commonly caused by trauma and/or severe bacterial infection. Army personnel have added risk, since wounds in combat zones are likely to become heavily contaminated. Furthermore, Army personnel are also at an increased risk to suffer burns and inhalation injuries that also lead to ARDS. The proposed project is exploratory. The long-term goal is to harness the property of viruses to induce cellular functions that may protect the individual from deleterious effects of ARDS. The main objective is to test this strategy on laboratory animal models for ARDS. When a virus infects a human cell, it struggles to modify multiple cellular functions in order to facilitate its own propagation. Such virus-induced functions may be beneficial to overcome inflammation and cell damage, which occurs in ARDS. The viral elements that induce these functions reside in its outer shell, termed capsid. It has been recently reported that empty capsids (shells) of a certain virus, called SV40, protect an experimental mouse-model against critical kidney injury by arresting the extensive damage that occur in their kidney cells. Survival and cure of the disease-model mice was impressively increased from 10% to over 60%. It should be pointed out that empty capsids are expected to be harmless, since they do not contain the viral genetic material that is required for its growth and propagation, suggesting minimal side effects of this therapeutic strategy. The present project aims at investigating the properties of such empty capsids for protection and treatment of ARDS. In addition, it will include basic scientific investigations on the molecular mechanisms of the activity of the capsids. This is essential for improving the therapeutic properties of this reagent and for designing better drugs. The innovation of this proposal is in its novel concept of drug development, which is based on using viral capsids for eliciting a combination of beneficial cell responses. While most drugs are aimed at a single cellular target, this concept provides a "multi-target" approach towards the treatment of the multifaceted condition of ARDS and other organ failures. Demonstration of beneficial effect of these viral capsids will constitute groundwork for future development of a novel therapeutic strategy for ARDS and is expected to provide a breakthrough in ARDS prevention and treatment. Subsequent studies will be directed towards progressing to clinical trials. In addition, the potential of these capsids for treatment of inhalation injury will be tested. Trauma and inhalation injuries are prevalent risks to which Army personnel are exposed in combat zones. Whole body inflammation caused by severe bacterial infection is a main cause for lung dysfunction in ARDS in the general population, including the Army, Veterans, and kin. The unique and novel concept of application of viral capsids as means of inducing multiple beneficial cellular functions is anticipated to stimulate additional studies on therapeutic qualities of capsids of other viruses.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510125
Entities
People
- Ariella Oppenheim
Organizations
- Hebrew University of Jerusalem
- United States Army