On Medicine

With research, possibilities are limitless- Rare Disease Day, 2017

In recognition of Rare Disease Day, Orphanet Journal of Rare Diseases Editor-in-Chief Ségolène Aymé discusses the importance of research in working to cure these diseases, the paradoxes sometimes presented in this effort, and the usefulness of direct patient participation.

Ségolène Aymé 27 Feb 2017

Pixabay, Hermann Traub

The tenth annual Rare Disease Day is celebrated on the last day of this month, Tuesday, 28th February. The theme of each year’s edition reflects a focal point of activities at the political level, to highlight the expectations of the community and the action items that need to be implemented to improve the quality of life of patients.

In 2017, the theme of research is being celebrated in hundreds of major cities and by institutions like the Orphanet Journal of Rare Diseases, which was established to support the publication of quality science, directly transferable to bedside care or policy making. This year’s slogan is apt and true, “With research, possibilities are limitless”, but it is not as straightforward as it sounds.

The current state of research and development is paradoxical. Science can now reveal the etiology and physiopathology of many rare diseases which were only described clinically in very few patients, mainly through a genomics-based approach. As of today, 3,200 genes are now linked to 4,500 diseases. This is extraordinary but the diagnosis of rare diseases remains suboptimal in most countries, for scientific and economic reasons.

As of today, 3,200 genes are now linked to 4,500 diseases.

Science does not yet explain the origins of all rare diseases as many of them are not Mendelian, and for those which are, sequencing fails to identify the genetic mechanism in more than half of the patients whose DNA is analyzed. In addition, although the costs of sequencing are decreasing rapidly, it is still unaffordable for most healthcare systems. Research efforts are needed to explore potential novel disease mechanisms, such as diseases linked to non-coding variants or tissue-specific mechanisms due to inappropriate methylation, yet digenic of oligogenic inheritance.

Another research-based contradiction exists in the field of therapy development. Incentives put in place to convince the pharma and biotech industries to invest in this area, have proved efficient. Over 450 rare diseases benefit from a marketed product, either in the USA or Europe, and the pipeline is promising- perhaps too promising, as the impact of orphan drugs on the pharmaceutical budget of countries is challenging their sustainability. Pricing and reimbursement is becoming the main topic of discussion between stakeholders, as the current model is not adapted to the avalanche of new products to be proposed.

It would not be ethical to neglect the funding and security of research and development, but this requires a lot of creativity as new economic models have to be proposed. A new distribution of roles between academia and industry has to be foreseen to decrease the cost of research, as the regulatory pathways have to be adapted to this new reality, and the way health technology assessments are conducted has to be modified to take into account the uncertainty raised by rarity.

Over 450 rare diseases benefit from a marketed product, either in the USA or Europe.

Rare diseases serve as an experiment for the organization of the healthcare system, for the field of innovation and for the values on which we want to base our choices. They are a stress test for our society.

Fortunately, rare disease patients themselves have played a major role in putting their illnesses on the political agenda, by motivating researchers to focus on their major unmet needs and in pushing the clinicians to share their expertise and network at an international level.

Patients have succeeded in reminding us that they should be at the center of all processes. By combining the research gained directly from patients, and the research acquired through innovation, “With research, possibilities are limitless” will continue to transcend its status as a slogan and serve as a real rallying call for the treatment of rare diseases.

Ségolène Aymé

Ségolène Aymé is a medical geneticist and the founder of Orphanet – a portal for information on rare diseases and orphan drugs. She is also the chair of the Topic Advisory Group on rare diseases at the World Health Organization, as well as European Union Committee of Experts on Rare Diseases. Dr. Aymé and is the editor-in-chief of Orphanet Journal of Rare Diseases (OJRD).