Rare diseases: maintaining momentum

Abstract

Despite having a low prevalence, rare diseases affect more than 300 million people worldwide. Almost half of these diseases are neurological, and 90% of rare childhood disorders have major neurological effects. Rare CNS disorders are often difficult to diagnose and treat, particularly as screening tests, diagnostic genomic sequencing, and specialist clinical expertise are not widely available. These challenges have been compounded during the COVID-19 pandemic, which, in Europe, resulted in more than 80% of patients having essential consultations cancelled. Nevertheless, there is cause for hope. According to a new report from Global Genes, a leading rare disease advocacy organisation, investment in rare diseases is gaining momentum. In 2021, drug developers invested a total of US$22·9 billion for research on rare disorders, an increase of 28% compared with 2020. Rare Disease Day, on Feb 28, 2022, signals a time to celebrate progress in research and advocacy efforts, and to reflect on the ongoing challenges. Research progress is gaining momentum too. For instance, a major unmet need has been the development of accurate and cost-effective tools to diagnose genetic disorders caused by repeat expansions, such as myotonic dystrophy, Huntington's disease, Friedreich's ataxia, or spinocerebellar ataxias. Now, new findings show that integration of whole genome sequencing into routine clinical practice could substantially increase the diagnosis of these diseases. On top of its high sensitivity and specificity for the detection of repeat expansions, whole genome sequencing can also identify repeat expansion disorders in previously undiagnosed patients. Other diagnostic and therapeutic challenges are also being addressed. The International Rare Diseases Research Consortium (IRDiRC), a public–private partnership, aimed to achieve two main objectives by 2020: to diagnose most rare diseases and to deliver 200 new therapies. The latter goal was achieved in 2017, 3 years ahead of schedule, and the goal for diagnostics is within reach. Looking to the future, IRDiRC have set three new ambitious targets for the next decade: for all patients coming to medical attention with a suspected rare disease to be diagnosed within 1 year and all currently undiagnosable individuals to be able to enter a research study; for 1000 new therapies for rare diseases to be approved; and for methodologies to assess the impact of diagnoses and therapies on patients. Through the work of ongoing and new multi-stakeholder initiatives, these targets are within reach. One such initiative is the Patient Identification and Engagement for RARE CNS Disorders (PIE4CNS) multi-stakeholder initiative, which aims to address barriers to timely diagnosis and to engagement of patients with clinical research in gene therapy and other promising novel technologies. A challenge will be the inclusion of patients from diverse ethnic backgrounds, particularly groups that are often under-represented in clinical trials. As part of the initiative, three workshops will be held to explore the challenges that might arise. The initiative plans to produce a report in Spring 2022, with specific recommendations informed by the outcomes of the workshops and from findings of surveys of patients, caregivers, and clinicians who treat rare CNS disorders. Collaboration is essential to avoid geographic or disease-based silos. In this respect, the European Reference Networks have been instrumental in facilitating the exchange of knowledge between health-care professionals across borders, ameliorating diagnosis and care, and will also be helpful to facilitate recruitment of patients across countries for future trials. However, a new policy framework is needed at the European level, to build on existing European health and research programmes and to guide the implementation of national plans and national strategies across all countries in Europe. EURORDIS-Rare Diseases Europe, a non-profit alliance of 962 rare disease patient organisations from 73 countries, is campaigning for a European Action Plan on rare diseases. The Rare 2030 Foresight Study, led by EURORDIS-Rare Diseases Europe, has set out eight recommendations as a roadmap to achieve long-term integrated European and national plans and strategies over the next decade. Action is needed to maintain momentum in investment and research progress in rare neurological disorders. Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation studyIn our study, whole genome sequencing for the detection of repeat expansions showed high sensitivity and specificity, and it led to identification of neurological repeat expansion disorders in previously undiagnosed patients. These findings support implementation of whole genome sequencing in clinical laboratories for diagnosis of patients who have a neurological presentation consistent with a repeat expansion disorder. Full-Text PDF Open Access