Oxford Biodynamics PLC (LON:OBD) Director of Business Development and Head of Statistics Dr Ewan Hunter caught up with DirectorsTalk for an exclusive interview to discuss the recent published study in the Journal of Translational Medicine
Q1: You’ve just had a study published in the Journal of Translational Medicine, can you provide a summary of this paper?
A1: So, this is a collaboration between Oxford Biodynamics and the Scottish Early Rheumatoid Arthritis cohort in Scotland which is managed through Glasgow University. What we have done there is utilised our EpiSwitch platform to develop chromosome conformational signatures from blood in pre-treatment patients for early rheumatoid arthritis to look at the likelihood of response to the first line disease-modifying anti-rheumatic drug methotrexate.
The study successfully showed that using blood, and measuring those conformational signatures in blood, we were able to find a signature which will able to differentiate between non-responders and responders to methotrexate, with a high degree of accuracy. This was based on our proprietary EpiSwitch platform which has been developed over the course of the company.
Q2: What do you think the impact of this paper is in regard to precision medicine?
A2: The ability to a pre- determined clinical response to therapy in any disease indication if you wish to choose a phrase ‘the holy grail of precision medicine’ and this study using chromosome conformational signatures offers the first evidence of using this type of data modality for determining response to therapy before patients have seen therapy.
Chromosome conformational signatures offer a first-degree view of deregulation on the genome, it’s currently not capable via established molecular modalities like gene expression. This research is the first evidence that using systemic measurement of chromosome conformational signatures is capable of addressing the needs in precision medicine for patient selection and tailored therapies.
We are also doing two projects currently undergoing in Oxford Biodynamics using the same approach to determine the response to checkpoint inhibitors. When the results from this study are public, this will cement the use of the EpiSwitch platform for precision medicine.
Q3: How does this work fit into the landscape of chromosome architecture, the regulation of gene expression and the control of the genome via the non-coding genome?
A3: This is now a new field and what we’ve seen over the last few years is the way of evidence indicating the role of chromosome architecture, or chromosome conformations, playing the regulation of the genome.
The level of information is expanding impressively, in two recent papers, one in Nature Communications by Gaëlle Marteil and another in Nature Genetics by Di Iulio et al with Craig Venter as the senior author, have shown that the non-coding genome is responsible for the regulatory control of the genome via chromosome architecture or chromosome conformational signatures.
In the Di Iulio/Venter paper, they were looking at the constraints of the human genome based on a human variation and what they found is that the clinical relevance in their study is that the manifestation of, enrichment of, pathogenetic variants in the constrained genome is identified by chromosomes architecture which we are measuring with EpiSwitch. They have suggested that pathical implementation of their findings in the targeting of sequencing effort beyond the exome so instead of looking at a gene, they’re suggesting that many exomes could be eliminated from targeted analysis by including the equivalent amounts of sequence it represents the most non-coding region which is ultimately where chromosome architecture occurs.
Q4: How are Oxford Biodynamics going to extend this work?
A4: So, we’re currently have two programmes going with the extension of rheumatoid arthritis work so we’re extending the project into a couple of hundred more patients from other medical facilities in the UK, that will look at independent validation of the signature that’s been published.
We’re also working with three other medical institutions in the UK; Glasgow University, Newcastle University and Birmingham, in Glasgow we’re already looking at a project, that’s already funded, looking at rheumatoid arthritis flaring. This is where patients basically go into remission after therapy with maybe drugs like methotrexate but with time, their disease flares up and currently there’s no molecular test can look at that. The project name for that is Biological Factors that Limit Sustained Remission in Rheumatoid Arthritis or the BIO-FLARE study, this project has started and we’re currently taking patients and we’ll begin later in the year on the EpiSwitch part of the study.