Francesco Frezzetti describes how the anti-shock drug was recently applied during the Ebola outbreak in West Africa, and outlines further potential scenarios for life-saving measures in emergencies
A white blood cell engulfing a bacteria. The new drug, TCS10, has been shown to block a cytokine storm during deep haemorrhagic shock and surgical trauma (photo: 123rf/Sebastian Kaulitzki)
Italian military research, conducted by the framework convention composed by the Defence Ministry and the university spin-off Health Ricerca e Sviluppo (HR&S, Italy) within the National Plan of Military Research, has recently tested the clinical lifesaving anti-shock effects of a melanocortin-based drug. This drug’s main mechanism of action is related to a peculiar antagonist of Systemic Inflammatory Response Syndrome (SIRS), complication that plays a major role in acute mortality rate and delayed-onset lethal complications in the shock-affected person.
According to the phase III of the clinical trial, this drug, named TCS10, showed safety and effectiveness in treatment of critically ill patients with very high survival rate and low delivery of blood transfusion. Such clinical outcome was associated with blocking a cytokine storm during deep haemorrhagic shock and surgical trauma, without any notable side effect.
Cytokine storm is the layman's term for a cytokine cascade or hypercytokinemia, essentially an overactive immune response. This is when a body detects foreign micro-organisms indicating an infection and responds by over-protecting the site of infection, producing and sending so many antibodies to the site that they collect in a cytokine storm. The primary symptoms of cytokine storm are high fever, redness, extreme fatigue and nausea; in some cases the immune reaction may be fatal.
TCS10 is currently undergoing final market procedures under the control of the Regulatory Affairs by the Defence Agency Industries.
The drug shows promise for treating medical conditions such as 'crush syndrome' caused by entrapment in rubble after an earthquake (photo: Ratindra Khatri, Nepal earthquake)
Despite the fact this research was conducted for clinical dual-use purposes – military and civilian – the effectiveness of TCS10 prompted the exploration of new potential for a first-strike drug in all settings in which tactical combat casualty care is applied, including disaster scenarios where different kinds of shock can frequently be observed.
As highlighted in the 2012 guidelines of the International Search And Rescue Advisory Group (INSARAG), medical conditions such as ‘Crush Syndrome’, caused by entrapment under rubble after an earthquake or other type of sudden onset disaster, can easily lead to shock and lethal delayed complications if not promptly treated.
Considering the capacity of TCS10 to expand the time window in which first medical care can be successfully provided in case of oncoming shock, HR&S researchers designed a new track- and- trigger- system and right- setting- first time by estimating and analysing the gaming scenario during a mass-casualty event. Data modelling showed the high life-saving impact of the drug applying different logistic solutions to existing policies both of ‘stay and play’ and ‘scoop and run’.
But cytokine storm is observed not only in the case of trauma-related sudden-onset disasters; this type of complication is also typical of severe infections and diseases such as Ebola and other kinds of haemorrhagic fevers, as highlighted in a video published by The Guardian on 22 October 2014 (see below).
The first months of 2014 signalled the beginning of the worst outbreak of Ebola Virus Disease (EVD) or, indeed, of any haemorrhagic fever in history. During this epidemic, over 11,300 people died, mostly in West Africa, from haemorrhage, shock, and multiple organ failure resulting from cytokine storms being the major cause of death.
Being aware of the characteristics of TCS10, HR&S, the Defence Agency Industries, and the Ministry of Defence agreed to start using TCS10 as life-saving medicine in Sierra Leone. On November 20, a 50-year-old male physician started showing the first symptoms of EVD contracted while working with Emergency in Sierra Leone. He was promptly repatriated and hospitalised at the National Institute for Communicable Diseases (INMI) ‘Lazzaro Spallanzani’, a Scientific Research and Health Care Institute (IRCCS) in Rome, the Minister of Health and the Italian Pharmaceutical Agency authorised the use of melanocortin in the treatment of EVD, in order to control the cytokine storm.
Initially the patient’s immunological condition was critical; however, on day five a steady improvement of his immune system was recorded, likely due to the administration of the melanocortin. The results were presented in a public lecture by Prof. Ippolito, the Scientific Director of INMI Lazzaro Spallanzani.
Although preliminary, the results so far obtained with the use of TCS10 highlighted potential new applications and scenarios in the field of disaster response. However, further applied research is needed to ensure that context-specific and resource-based constraints are accounted for, allowing for the definition of new models and games in the field of health in emergencies.
Francesco Frezetti is Disaster Management specialist, Master of Disaster Management from University of Copenhagen
Edited by Ian Portelli
The Italian Ministry of Defence as of EF a 2011.188 National Plan of Military Research produced crucial support to the research.
Special thanks go to Prof. Giorgio Noera, Dott. Claudio Camerino, and Prof. Alfio Bertolini [leading researchers and investigators of Health Ricerca e Sviluppo] who dispensed insight and expertise, assisting the conclusions of this paper.
Additional thanks go to Giancarlo Anselmino [Director of Defence Agency Industries] for support and for providing necessary guidance, concerning the implementation of the research projects.