Cystic fibrosis drug trialled to fight inflammation caused by COVID-19
10 July 2020
Patients with COVID-19 will be given the cystic fibrosis drug ‘Dornase alfa’ to determine if it can help improve survival by reducing excess inflammation in the lungs, as part of a trial co-led by UCL and the Francis Crick Institute.
The COVASE trial has been funded by LifeArc, a medical research charity, and will be run in partnership with University College London Hospitals (UCLH) NHS Foundation Trust. Up to 40 patients are expected to be recruited.
During a viral infection, a group of white blood cells called neutrophils release neutrophil extracellular traps (NETs*) which are extra-cellular meshes whose primary role is to trap and kill bacteria. Researchers believe the immune system in COVID-19 patients is over-active and an abundance of NETs could be causing excess inflammation (hyperinflammation) and contributing to the onset of pneumonia and severe damage to the lungs.
In the trial, select hospital patients will be given Dornase alfa twice a day for seven days and researchers will examine the drug’s effect on inflammation and survival. Historic controls will be derived from an existing database of 120 subjects with COVID-19 who have been admitted to UCLH since the beginning of the outbreak.
Chief Clinical Investigator, Professor Joanna Porter (UCL Medicine) and Consultant in Respiratory and General Medicine at UCLH, said: “Hyperinflammation is an overreaction of the body’s immune system, which can cause serious breathing problems and has proven to be one of the most fatal conditions in those with severe COVID-19.
“Dornase alfa has an excellent safety profile and has been used for many decades to help breakdown mucus secretion in the lungs of patients with cystic fibrosis.
“Similar mucus secretions, along with cellular debris from NETs, have been seen in patients with COVID-19, so we are hopeful this drug can have a similar positive effect reducing inflammation and enabling patients to be discharged from hospital earlier than they would have been without the treatment.”
This trial is based on research by Dr Venizelos Papayannopoulos at the Crick. His lab has already identified specific damage-associated molecular patterns (DAMPs) in NETs that are responsible for excess inflammation during infection. The trial aims at clearing these DAMPs using Dornase. Therefore, the Crick lab will be monitoring the effect of the treatment on the presence of these DAMPs and the impact on inflammation in patients on the trial.
Dr Papayannopoulos said: “We’ve spent years studying how the immune system interacts with microbes to protect against infection but also, what happens when these responses are deregulate to promote disease.
“The challenge at hand is to use this information in order to tackle excess inflammation in the lungs of patients with COVID-19. We hope to reduce the amount of time people spend in hospital and the number of patients who require intensive care.”
Dornase alfa, has been approved since 1994 for the treatment of cystic fibrosis (CF), an inherited condition that causes mucus to build up in the lungs. The drug is delivered directly to the lungs as patient’s breathe in a mist created by a nebuliser. In CF patients it has been shown to reduce NETs and inflammation, reduce the risk of developing a respiratory tract infection, and improve pulmonary function.
The drug can be self-administered at home and so if shown to be effective in hospital, could also benefit people with COVID-19 who have mild disease and are self-isolating, or those who have been discharged from hospital to continue their recovery at home.
This study is being supported by a grant from the medical research charity LifeArc, as part of its activities to address the need for new therapies for Covid-19. LifeArc has made £10m available to repurpose existing medicines or those in the late stage of development as this approach offers one of the fastest routes to develop new treatments that could tackle the virus and its impact.
The Dornase alfa will be administered using the PARI eFlow®Rapid electronic nebuliser, kindly donated by Pari.
Support for the COVASE study design and protocol was provided by the statistical analysis specialists, Exploristics, and by drug discovery and development consultancy, Target 2 Treatment.
*Neutrophils are among the first immune cells recruited to sites of infection, undertaking several strategies to eliminate the invading agents. Neutrophils engulf and kill microbes intracellularly and release antimicrobial factors that combat pathogens extracellularly through degranulation and the release of neutrophil extracellular traps (NETs). NETs are extra-cellular meshes whose primary role is to trap and kill bacteria. However, NET overabundance is also linked to inflammatory and autoimmune disease.
- Professor Joanna Porter's academic profile
- UCL Medicine
- Dr Venizelos Papayannopoulos
- The Francis Crick Institute
- Clouded areas in X-ray of lungs depict pneumonia infection. Credit Dr Vicky Enne
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