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Together rare disease They affect more than 200 million people worldwide. However, due to its low frequency at the individual level, this disease is a challenge for medicine. Fortunately, developments in genetics and genomics in recent years transformed the scenario of so-called “diagnostic wandering” into rarer diseases. They are better known at the clinical and genetic level and better tools are available for their diagnosis, such as genome sequencing. This situation has opened up new opportunities for precision medicinethat enhances patient care from a personalized perspective, taking into account their clinical, genetic and lifestyle characteristics.

The most recent review, published in Journal of Internal Medicinereview current state of precision medicine in rare diseases. In it, twelve professionals from different institutions discuss the evolution of precision medicine in the diagnosis and treatment of rare diseases, as well as the challenges of its application and emerging technologies in this field.

European initiative for precision medicine in rare diseases

Paradigm shifts in the diagnosis and treatment of rare diseases have resulted in many countries starting to differ a precision medicine initiative that proposes genome sequencing as a first-line method for the diagnosis of rare diseases. Among them, the United Kingdom stands out, which started its career as a pioneer of genomics in Public Health in 2012. On the European scene, there are also precision medicine initiatives in Germany, Sweden, France and, more recently, other countries such as Spain. This review discusses the first initiatives as well as progress and the current situation.

The evolution of precision medicine for rare diseases

From Sanger sequencing to today’s massive DNA sequencing techniques, there have been a series of advances that have made the incorporation of genomics into clinical practice possible. Current existing different analysis strategies (gene panel, exome, genome) selected by professionals according to patient characteristics or available resources in the center or health system.

The trend is heading whole genome sequencing as the first diagnostic test, experts say. The overview presents a workflow with the expected diagnostic results with this approach. For example, it is expected that 40% of patients receive a molecular diagnosis, 10% are carriers of a variant of uncertain significance, and approximately 1% have a secondary outcome, relevant but unrelated to the original clinical condition. In the case of undiagnosed patients, periodic review of results, as new knowledge is gained, can facilitate later diagnosis.

Another interesting point that the review highlights is that clinical geneticists are no longer the only ones requesting genetic testing. Other specialists such as cardiologists, oncologists or pediatricians are also increasingly in demand.

In medicine, the second major focus of precision medicine, experts point out precision treatments are already available for around 500 rare diseases. They also highlight that molecular diagnostics is necessary for many of the targeted therapies that have been approved or are being developed.

Implementation of precision medicine for rare diseases in clinical practice

With the recognition of the potential of precision medicine, the next logical step would be promote its application in clinical practice. In this regard, the authors of the reviews highlight the role of education in genetics And Collaborative work international organizations and the various agencies involved.

Regarding education, the review highlights the enormous effort involved in the education and training of health professionals, both now and in the future. “The systematic incorporation of genomics and precision medicine into the curriculum of preparation of all health professionals is critical to understanding that the next generation of health professionals is trained in the management of genetic information every day,” they said.

The future of precision medicine

Finally, the review discusses popup method which will complement genome sequencing to improve the diagnosis of rare diseases. Among them, the importance of sequencing long DNA fragments, RNA sequencing and methylation analysis and other epigenetic mechanisms stands out.

They also point to the urgent need to develop tests that systematically determine the functionality of the thousands of variants that exist in databases but have not yet been classified as pathogenic or benign. In this regard, they mention various projects and strategies and highlight that responsible data sharing will be an important element for advancing the diagnosis of rare diseases.

“Implementation of genome sequencing on a large scale in clinical care requires a massive educational effort and a multidisciplinary approach to integrate multimodal data, including clinical, laboratory, and imaging investigations,” the review authors conclude. “Diagnosing all rare diseases is a very challenging task and success will depend on innovative approaches, data sharing, monitoring results linked to precision therapy and close collaboration with patient groups.”

Scientific articles: Tesi B, Boileau C, Boycott KM, Canaud G, Caulfield M, Choukair D, Hill S, Spielmann M, Wedell A, Wirta V, Nordgren A, Lindstrand A. Precision medicine for rare diseases: What’s next? J Intern Med.2023 May 21 doi: http://dx.doi.org/10.1111/joim.13655.

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