Pathogen Genomics Unit
The Pathogen Genomics Unit (PGU), led by Professor Judy Breuer, was established at UCL in 2016 with funding from the UCLH BRC and Medical Research Council. When it was conceived the PGU was the only dedicated pathogen sequencing service in the UK and is now a leading pathogen sequencing service currently able to routinely sequence the whole genomes of 14 different viral species and can sequence bacteria from any bacterial isolate. Since the start of the COVID pandemic the PGU has played a vital national, and international, role in the fight against Covid-19.
The PGU hosts the London hub of COG-UK, rapidly sequencing whole genomes of SARS-CoV-2. Supporting nine hospitals across London for sequencing Covid-19 samples the PGU has so far generated over 15,000 sequences, providing important data to hospitals and Public Health England on how the virus spreads to help inform local and national policy and decision making around social distancing measures and lockdowns. Data produced from the analysis of these sequences were fed back to SAGE and the Joint Committee on Vaccination and Immunisation (JCVI) to influence national decision making. This is the first demonstration that rapid pathogen sequencing can be used to directly impact public health in real time. UCLH were the first site to recruit to the Hospital-Onset COVID-19 Infections (HOCI) observational clinical trial which is led by the PGU.
HOCI is evaluating the utility of pathogen sequencing for the management of hospital acquired infection aiming to break the chain of virus transmission (reporting July 2021). Recently the PGU was announced as a scientific partner to Halo, a Covid-19 testing company contracted by the government to provide PCR tests on passengers landing in UK airports from around the world. The PGU will carry out rapid sequencing of viruses that test positive for Covid-19.
BEAT-LUPUS
Work by Professor Mike Ehrenstein underpinning novel clinical trials in Systemic Lupus Erythematosis (SLE) and other rheumatological diseases led to the 2014 launch of a phase II interventional clinical trial examining the safety of belimumab (BEAT-LUPUS) after rituximab. SLE is an autoimmune disease characterised by periods of illness “flares” interspersed with periods of wellness or remission and affects around 1 in 2,000 people in the UK.
Rituximab is a biologic drug used to treat patients who don’t respond to conventional treatment, by reducing the number of B-cells that causes inflammation in lupus. Rituximab shows some benefit for people with lupus. For some patients, however, inflammation can flare up again. Belimumab is a drug that targets BAFF (a protein which increases the number and activity of B-cells) to keep the number of inflammatory B-cells under control and reduce lupus flares. Belimumab is licensed in the UK to treat lupus but it is not used often in the UK.
In BEAT-LUPUS, belimumab was given to patients after they had received rituximab. BEAT-LUPUS completed in 2020 after successfully recruiting 52 patients to what was the first ever academic early phase randomised control trial in rheumatology, and the first trial testing a combination of biologics for SLE. The trial was funded by Versus Arthritis, GSK, NIHR Musculoskeletal Translational Research Collaboration and the UCLH BRC. The results of BEAT-LUPUS have demonstrated that:
- Treating people with belimumab after rituximab caused a reduction in blood levels of IgG anti-dsDNA antibodies which are associated with disease activity in lupus.
- Belimumab after rituximab led to a threefold reduction in severe flares in patients with lupus compared with the placebo group.
- Belimumab suppressed the number of B-cells at 52 weeks compared to the placebo group.
These results are very promising and will pave the way for a larger phase III study. The results of this study will also be submitted to NICE and are expected to change the guidance for treatment of SLE.
Enhanced Liver Fibrosis Test
Co-invented by Professor William Rosenberg, the iQur a team developed a leading, non-invasive liver fibrosis test, the Siemens Healthineers Enhanced Liver Fibrosis (ELF) test. The ELF test can detect the pre-symptomatic stages of liver fibrosis (Peveler et al., Adv Mater 2018) and has been awarded FDA and NICE approval, with major impact in reducing unnecessary hospital referrals, clinical investigations and therapy.
BioAid
The BioAid project is a cross- BRC collaboration with Imperial, Kings College and University Hospital Birmingham which aims to create a registry of 10,000 adults presenting with infectious disease, and link clinical phenotype and microbiological data to host DNA, RNA and plasma biobanking.
By evaluating the usefulness of genomic, transcriptomic and proteomic analysis, the aim is to identify and validate novel biomarkers for clinical use within the next five years.
This will be the largest ever prospective sample and data collection of patients with suspected infectious diseases globally.
