© Dorota Badowska

The RD-CONNECT project is linking up databases, biobanks, registries and other valuable resources in support of research into rare diseases. The platform created by the partners is global in scope, encouraging scientists to contribute and access data from around the world. Tools enabling them to explore and process this material have also been developed.

The platform already holds genomic and clinical information for thousands of patients, says project coordinator Hanns Lochmüller of the UK’s University of Newcastle upon Tyne. It allows scientists to match up individuals likely to be affected by the same illness – who may well live in different countries, and whose similarities might otherwise have gone unnoticed – and compare their genomes to pinpoint a shared variation that may have caused the disease.

As of September 2017, RD-CONNECT had helped to identify more than a hundred such genes, Lochmüller reports, and it doesn’t intend to rest on its laurels. The discoveries it is helping to deliver are underpinned by powerful new technology: the possibility of sequencing a patient’s entire genome – or exome, if the non-coding parts of the genes are excluded – quickly and affordably is a very recent advance.

This development widens the scope to provide accurate and timely diagnoses, and generate leads for the development of treatments. By facilitating work in both areas, the activity deployed in RD-CONNECT advances the objectives set out by the International Rare Diseases Research Consortium (IRDiRC).

The benefits of sharing

Building a platform that draws on patient information held in a wild variety of formats, in many different locations and in highly diverse regulatory environments, is unlikely to ever be a straightforward process. And yet, addressing the technical, legal and ethical aspects of this undertaking was only part of the challenge, Lochmüller notes.

“Often, the main bottleneck is concern about the implications of sharing data,” he observes, adding that RD-CONNECT’s success in creating confidence in this approach is one of the project’s greatest achievements. “We have shown in a practical way that all stakeholders benefit. The clinicians get a better diagnosis for their patients, industry can use the data to develop drugs, and of course scientists produce better papers when they collaborate.”

And, first and foremost, “patients benefit by obtaining a diagnosis – we have quite a few examples where individuals were enrolled in clinical trials based on the findings that we obtained,” he observes. “For some, the diagnosis even gave them access to an existing treatment.”

Every such advance chips away at a vast, largely unresolved issue: the scarcity of treatments for the many rare diseases identified so far. More than 7 000 such illnesses are known, which means that rare diseases, considered collectively, are not actually uncommon. According to estimates, about 30 million people are affected in the EU alone. Many of them may never have received a conclusive diagnosis.

Exomes and beyond

This combination of details about patients’ genetic make-up and precise, computer-readable information about the way their disease affects them physically and physiologically is one of the platform’s particular strengths, Lochmüller notes.

“The more exome and clinical data is entered into the database, the more useful it gets, because the likelihood of finding matches increases,” he says.

Doctors can often intuitively see when one patient is similar to another. RD-CONNECT brings the power of computers into that process so that it can happen across centres and continents.

However, Lochmüller observes, rare diseases of genetic origin are not necessarily linked to a single variation. There could be several genes involved, for example.

“And in some cases, more complex mechanisms are likely to be at play,” he explains. “For these, we need additional information.”

Approaches such as transcriptomics or proteomics – where scientists look at a patients’ RNA or proteins – could yield valuable clues. The partners have therefore begun to include further –omics information that may be available for individual patients, Lochmüller says. The upgraded platform will notably underpin research in Solve-RD, a follow-on project also funded by the EU.