p47-CGD is a rare genetic disorder in which the ability of immune cells to clear infections is compromised. As a result, patients with p47-CGD suffer from recurrent, severe and life-threatening bacterial and fungal infections, as well as widespread tissue inflammation. The severe infections can include skin or bone infections and abscesses in internal organs such as the lungs, liver or brain, and in some cases the immune over-activity causes inflammatory bowel disease.
Although improvements in infection control have seen significant increases in lifespan for patients with the genetic mutations underlying p47-CGD, lifetime antibacterials and antifungals are required, and even then patients repeatedly face hospitalisation for periods of 4-5 weeks at a time due to failure of prophylaxis. The only current curative therapy – bone marrow transplantation – is a risky option for many patients because of the scarcity of fully matched donors, and even then the procedure itself has a significant rate of complications.
Prof Thrasher and his colleagues at the UCL Great Ormond Street Institute of Child Health have developed a potentially curative, ex vivo gene therapy for p47-CGD, based on technology designed by Dr Santilli in-house. This is already in clinical trials in the US and Europe for the X-linked form of CGD and is showing very encouraging early results. In a number of preclinical experiments, Prof Thrasher and team have shown that their new gene therapy has the potential to restore normal immune function in p47-CGD. The funding provided by the UCLTF is intended to support completion of final preclinical steps and to take the therapy to a first-in-man, proof-of-concept clinical trial.
Support for this project is enabled by UCLTF’s innovative investment model. In addition to providing funding and commercial support for traditional university spinout companies, UCLTF also provides investment finance for translational projects which have significant commercial potential, by which funding is provided directly to academic labs such as Prof Thrasher’s team. This approach enables university research groups to de-risk technological development of their projects, carrying them through to a much later stage and increasing the probability of achieving more substantive licensing outcomes.