ULTRA-DD

There are many proteins that could potentially be targeted in autoimmune and inflammatory diseases like rheumatoid arthritis, lupus and Sjögren’s syndrome. The problem is that a lot of research needs to be done to find out which proteins are good targets while also being amenable to treatment with molecules. The ULTRA-DD project was set up to make some headway in identifying which proteins are worthy candidates for further study, ###in the hope that the publicly-available knowledge they generate will lead to future clinical trials for new drugs.

The tools and data generated by the project are being made available open access, said project coordinator Michael Sundström. ‘None of our outputs are patented and there are no restrictions on its use for the research community. The industry partners won’t have exclusive rights to any of it; the databases, websites and publications are in the public domain in various open repositories, so everybody can benefit from the discoveries we’ve made and the research tools we’ve generated, long after the project ceases to exist.’

The project is already aware of widespread use of the research tools in the community. ‘We've been disseminating the chemical compounds that we developed to several hundred research groups across the globe,’ said Dr Sundström. ‘We have made arrangements with chemistry vendors that they will provide these compounds to the community for a nominal or reduced fee, long after the project is closed. With time, we will probably disseminate to several thousand research groups.’

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The ULTRA-DD project has published details of an antibody against interleukin-8 that can be used in research on diseases such as rheumatoid arthritis. By making the sequence and other details public through open access, the team hopes that other researchers will be able to use them and adapt them for their own research.###

In our bodies, our immune system produces antibodies to defend us from infectious diseases. It is also possible to produce antibodies in the lab. In some cases, these are used as treatments for disease. While the quality of these treatment-grade antibodies is very high, they are protected by intellectual property rules and so their use in research is limited. Many more antibodies are used in drug development, to study possible drug targets for example. However, the quality of these research-grade antibodies is often poor, and this makes results generated using them unreliable. One major problem in the world of antibodies is the reluctance of some researchers to publish the sequences of antibodies they develop.

Now, ULTRA-DD is working to change this situation. They are using the latest techniques to generate and validate new antibodies in collaboration with the clinical research community and external commercial partners and are publishing the results on the project website.

‘Our antibodies have their sequences revealed and they are open access, meaning that we want other researchers in companies and academia to pick them up and use them without restrictions,’ said the project’s Susanne Gräslund of Karolinska Insitutet. ‘As the sequences are known they can be easily converted to other formats and modified if needed.’

The first antibody released, against interleukin-8, will be primarily of interest to the rheumatoid arthritis field, but could also be relevant for researchers working on other inflammatory diseases and possibly also cancer. ‘We also hope that our project can serve as a good example for sharing sequences for antibodies and more openness in the field,’ concluded Dr Gräslund.

The ULTRA-DD project has made good on its promise to make its data open source with the publication online of datasets from experiments on autoimmune diseases such as lupus and myositis. ### Through the experiments, the ULTRA-DD team has identified potential new targets that could inspire the development of new treatments for these diseases. The project hopes that if other researchers probe and use the data, they may uncover further insights that will add to our knowledge of autoimmune diseases and accelerate the development of medicines for these patients, many of whom do not respond well to existing treatments. Currently, additional follow-up studies are ongoing to verify and validate the results.

The data published by ULTRA-DD comes from experiments using technically advanced tests developed by the project partners. In this case, the ULTRA-DD team studied so-called ‘B cells’ – immune cells which are known to play a central role in lupus and myositis. The project’s Scientific Director, Michael Sundström of the Karolinska Institutet says: ‘These are the first of a series of related datasets to be released, and we believe that our approach of pre-publication access to such data is truly unique.

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The Structural Genomics Consortium (SGC), one of the project partners in IMI’s ULTRA-DD project, won the 2016 Oxford Academic Health Science Network Public-Private Collaboration Award, for its pioneering work to accelerate drug discovery. The award celebrates innovative public-private collaboration among universities, industry and the National Health Service (NHS) that ultimately benefits patients.### The SGC was the unanimous winner chosen by an independent panel of judges. The judges noted that the SGC’s initiatives were of ‘significant scope and scale’ and ‘could make a significant difference.’ Upon receiving the award, Chas Bountra, the Chief Scientist of SGC Oxford, said: ‘The SGC in Oxford is working with pharmaceutical companies, biotechs, patient organisations, clinicians and academic researchers to identify new therapeutic targets. We have assembled this extensive network of expertise to generate high quality, freely available, novel reagents to accelerate drug discovery for patients. We are delighted to receive such a prestigious award.’ 

Patients already have a big role in many IMI projects, for example by helping with patient recruitment or advising on best practices in clinical trials.### Now the ULTRA-DD project is taking it one step further. In the past year, several patient organisations, including Myeloma UK and The Brain Tumour Charity, have committed to sponsoring postdoctoral researchers, whose scientific outputs will contribute directly to the ULTRA-DD project. The sponsorship of about €1.5 million for the next two years will be done through the Structural Genomics Consortium (SGC), one of the partners in ULTRA-DD. With this step, these organisations will become directly involved in the scientific aspects of the project, helping to speed up the development of medicines for diseases which they are most interested in. ‘There are more and more patient organisations taking the matter into their own hands from the early stage drug discovery to the clinical studies’, said Wen Hwa Lee of the SGC. ‘At the moment every foundation is trying to do something on their own, for their own disease. In our view, the best option would be to give these disease foundations access to an open research platform so they could be clustered around the ULTRA-DD project. We believe that could be the foundation of a completely different way of working that could enable faster drug discovery.’ The main goal of the ULTRA-DD project is to speed up the development of truly innovative medicines, especially in the areas of autoimmune and inflammatory diseases. Through the SGC, ULTRA-DD has strong ties with similar initiatives elsewhere in the world, and this, coupled with the project’s strong open access policy, will ensure that the tools generated by the project will benefit the entire scientific community.