Combined Cellular and HSD-1 gene therapy for ARDS

  • Research type

    Research Study

  • Full title

    A research study to investigate whether transgenic mesenchymal stem cells expressing hydroxysteroid dehydrogenase type-1 can attenuate inflammation in Acute Respiratory Distress Syndrome

  • IRAS ID

    204225

  • Contact name

    David Thickett

  • Contact email

    d.thickett@bham.ac.uk

  • Sponsor organisation

    University of Birmingham

  • Duration of Study in the UK

    3 years, 0 months, 0 days

  • Research summary

    When some people have a severe infection, their body's defence systems can over-react and cause damage to their own organs through a process called inflammation. When the lungs are damaged in this way, it is called acute respiratory distress syndrome (ARDS). ARDS causes the lungs to fill up with water, making it difficult to breathe. These patients need to be looked after in the intensive care unit (ITU), where a machine can support their breathing. The death rate is 30%.
    The body produces natural steroids which can reduce inflammation. These steroids are activated by an enzyme called HSD-1 (11beta-hydroxysteroid dehydrogenase type 1). We found that patients with ARDS have reduced levels of HSD-1 and reduced steroid activation in their lungs.
    We want to determine if stem cells which have been genetically modified to produce high levels of HSD-1 enzyme will have the ability to reduce lung injury in ARDS. We want to determine if this therapy could help treat patients with ARDS in the future.
    We want to take lung washings from patients with ARDS and from critically ill patients on breathing support in the ITU who are at-risk of ARDS. We will test the macrophages (one of the body's defender cells) from lung washings to see if their ability to reduce inflammation by clearing away dead cells is reduced in patients with ARDS (compared to critically ill at-risk patients). We will also test the genetically modified stem cells on macrophages to see if this improves their ability to clear away dead cells and bacteria. Blood and urine will also be taken for additional testing.
    Patients would be recruited from the University Hospitals Birmingham and Heart of England NHS Trusts over a 3 year period 2016-2019. This project is funded by a grant from the Medical Research Council.

  • REC name

    Wales REC 1

  • REC reference

    16/WA/0169

  • Date of REC Opinion

    22 Jun 2016

  • REC opinion

    Further Information Favourable Opinion