Partnering for progress: AMRC members and SGC Oxford By Eileen McNeill, Programme Manager: Disease Foundations, SGC Oxford Published: 28 August 2019 Every stakeholder in the chain from the patient, the clinician, the pharma company, to the laboratory scientist has a different perspective on the biggest challenges in treatment of a disease. How do we unite these voices to produce the most rapid progress? With their uniquely close relationship to all stakeholders, and laser focus on new medicines, medical charities and disease foundations have a great impact. Partnering with AMRC members helps other organisations benefit from this clarity of vision and purpose, whilst bringing their own perspective and skills. This partnering approach is something we as a disease agnostic organisation particularly value. The SGC (Structural Genomics Consortium) is an international Open Science consortium working with academics, charities and industry to catalyse research supporting early stage drug discovery. For SGC Oxford, based at the University of Oxford, partnering with disease-focussed charities allows us to direct our well-established scientific platforms into specific areas of unmet clinical need. Whilst our organisation is disease agnostic, our individual scientists are not, and relish the focus and input that partnering with charities and patient groups provides. From larger endeavours, such as supporting the establishment of The Alzheimer’s Research UK Oxford Drug Discovery Institute, to the defined results-driven projects highlighted below, partnering with disease-focused organisations helps us meet our shared aim of faster progress to new medicines. Producing high quality tools to accelerate drug discovery in new areas In the absence of information and tools for research on new potential targets, most research is directed at already well-explored options. We shine a spotlight on under-investigated proteins, by producing 3D structures, chemical tools and screening assays, enabling disease focused researchers to follow up investigations of new areas of biology, often highlighted by genomic datasets. For example, working out the physical shapes of normal and mutated proteins can provide clues as to why and how a protein causes disease, as well as to help scientists design better drug molecules. We also produce high quality ‘pharma standard’ small molecule inhibitors (Chemical Probes) to support cellular studies of these new therapeutic targets to accelerate drug discovery, working with our extended network of pharma and academic collaborators. By placing all our research outputs and reagents in the public domain, without restriction on use, these new data and tools can be rapidly utilised by researchers across the globe for downstream therapy development. This maximizes publicly available information speeding up discoveries by reducing duplication and the lost time and money that entails. Keeping science in the open so everyone benefits Our ethos, as passionate advocates of Open Science, matches closely the ethos of AMRC members. We have pioneered an open lab books initiative where our researchers post their experimental data along with a lay commentary online, so all stakeholders (collaborators, charities, donors and patients) can view and contribute to the progress of the project. As well as sharing our successes we also share our learnings from project difficulties, meaning others do not waste time or resources to encounter the same problems. We also put all our methods and reagents into the public domain, often before publication, driving our findings out into research communities as quickly as possible. Fine-tuning our focus in tailor-made partnerships Partnering with AMRC members and discussing your priorities and unmet needs have allowed us to work together to design novel projects and platforms. The Brain Tumour Charity has partnered with us for two projects. Firstly, to evaluate the therapeutic potential of our own set of Chemical Probes in patient derived cell lines, and secondly, to advance a known driver of Diffuse Midline Glioma (formerly known as Diffuse Intrinsic Pontine Glioma, DIPG), the BMP receptor ACVR1, into a drug development programme based on prior SGC knowledge and reagents. The Brain Tumour Charity partnership is enabling further cellular assays to complement ongoing efforts to produce a medicine targeting ACVR1 as part of a wider programme that has been taken forward by the world’s first Open Science drug discovery pharma company M4K pharma with whom we continue to work. We are pleased that this ongoing partnership with The Brain Tumour Charity is expanding to include input into the M4K pharma process too. It shows how our partnership has evolved and we are working together to accomplish real-world impact. Working with the Motor Neurone Disease Association (MNDA), and their international partners, we have established the ALS-RAP project –Amyotrophic Lateral Sclerosis Reproducible Antibodies Platform for the production and validation of novel and commercial antibodies. High-priority targets are nominated by their research community via the project website, which also gives real-time updates on the progress of the project. Our project will validate a truly robust set of mission-critical reagents benefitting both the MNDA and wider community. Myeloma UK highlighted compounds and relevant cells for a partnership to use our cutting edge chemoproteomics platform to characterise the intended and additional targets of experimental and existing treatments. Even the most specific drug is likely to have at least 6 binding targets once in a cell, which may be either beneficial and increase its efficacy, or cause side-effects limiting use in patients. This knowledge could drive improved future drugs and help understand why some patients don’t respond at all to current ones. Outside our links with AMRC members we work with other national and international disease foundations on early stage projects, such as those with the Chordoma Foundation and Galactosemia Foundation, through to clinical trials. Our first phase 2 clinical trial is beginning this year, to treat the ultra-rare disease fibrodysplasia ossificans progressiva (FOP) with a drug repurposing candidate, following a drug screening project at SGC and long relationship with FOP Friends. Looking to the future We are excited about the opportunities and outputs these partnerships have generated and are now looking for new partners. Working together we can produce the data and tools needed in your research communities. If you’d like to hear more about our work, or are interested in exploring some project or partnership ideas, please contact Dr. Eileen McNeill, Programme Manager (Disease Foundations), at [email protected] .