New medicines that work via novel, previously unexploited mechanisms are known as ‘first-in-class’ treatments and developing them is extremely challenging. Firstly, the early stages of drug development often involve tests using either simple cultures of human cells or animal models of diseases. However, these are often poor mimics of how diseases actually behave in humans, and positive results in these early studies do not always translate into safe, effective treatments for patients. Furthermore, even if reliable disease models are available, tools to study them in depth may be lacking. Finally, the expertise and resources required to develop these new tools is found in a range of different organisations; industry has experience of designing new tools, the clinical community has closer contact with patients and intimate knowledge of diseases, and the academic community typically has more expertise regarding the molecular biology of diseases.
By bringing together representatives of these different communities to create an open, collaborative partnership, ULTRA-DD was able to deliver the tools, resources and knowledge that will advance research, speed up drug development, and benefit the wider research community.
Focus on autoimmune and inflammatory diseases
A large part of the project was dedicated to developing research tools based on high-quality samples of cells and tissues from patients with specific diseases. These tools allow researchers to study diseases in depth. ULTRA-DD focussed on two important areas where safe, effective treatments are currently lacking: autoimmune and inflammatory diseases. Autoimmune diseases up for study in ULTRA-DD include systemic lupus erythematosus (SLE), idiopathic myositis, Sjögren’s syndrome, and systemic sclerosis. Collectively, these diseases are known as systemic inflammatory autoimmune diseases and they affect around 1% of the population in Western countries. Although their symptoms vary, they are all caused when the immune system attacks the body’s own tissues. There is currently no cure for these diseases and existing treatments are not effective in all patients and often come with unpleasant side effects.
The second disease category studied in ULTRA-DD is immune diseases that trigger damage to the bones and cartilage, such as fibrodysplasia ossificans progressive (FOP) and ankylosing spondylitis (AS). FOP is an extremely rare, currently-incurable condition in which bone forms in the muscles and soft tissues of the body. AS is a type of arthritis that mainly affects the spine is found in around 0.2% of the population. Again, more research is needed to find effective treatments for these devastating diseases.
Another part of the project is developing a suite of probes, tests and methodologies to study these disease-specific research materials in depth.
In addition. through project partner the Structural Genomics Consortium, ULTRA-DD worked closely with related initiatives carrying out similar work on neurological diseases and cancer.
In order to ensure the project results are taken up and used widely, ULTRA-DD operates an open access policy. The wider scientific community will therefore have ready access to much of the knowledge, data and tools generated by the project. Ultimately, the hope is that ULTRA-DD will dramatically increase our understanding of the underlying molecular causes of the diseases under investigation and so reinvigorate drug discovery pipelines.
This partnership met all of its objectives by generating protein based research tools (e.g. structures, assays), generating chemical and antibody probes and using patient-cell derived assays for target definition and validation. They made all their reagents and knowledge available through Open Source, significantly contribute to understanding of complex disease systems and promoting drug discovery and development.