Gene-targeted therapies: Towards equitable development, diagnosis, and access.

Genomic and gene-targeted therapies hold great promise in addressing the global issue of rare diseases. To achieve this promise, however, it is critical the twin goals of equity in access to testing and diagnosis, and equity in access to therapy be considered early in the life cycle of development and implementation. Rare disease researchers and clinicians must simultaneously recognize the life-altering potential of early diagnosis and administration of gene-targeted therapeutics while acknowledging that not everyone who experiences a rare disease and needs these therapies will be able to afford or access them. Achieving equity in the development of and access to gene-targeted therapies will not only require innovations in research, clinical, regulatory, and reimbursement frameworks, but will also necessitate increased attention to the ethical, legal, and social implications when establishing research paradigms and the translation of research results into novel interventions for rare genetic diseases. This article highlights and discusses the growing importance and recognition of health equity across the spectrum of rare disease research and care delivery.

Scaling genetic resources: New paradigms for diagnosis and treatment of rare genetic disease.

Development of genetic tests for rare genetic diseases has traditionally focused on individual diseases. Similarly, development of new therapies occurred one disease at a time. With >10,000 rare genetic diseases, this approach is not feasible. Diagnosis of genetic disorders has already transcended old paradigms as whole exome and genome sequencing have allowed expedient interrogation of all relevant genes in a single test. The growth of newborn screening has allowed identification of diseases in presymptomatic babies. Similarly, the ability to develop therapies is rapidly expanding due to technologies that leverage platform technology that address multiple diseases. However, movement from the basic science laboratory to clinical trials is still hampered by a regulatory system rooted in traditional trial design, requiring a fresh assessment of safe ways to obtain approval for new drugs. Ultimately, the number of nucleic acid-based therapies will challenge the ability of clinics focused on rare diseases to deliver them safely with appropriate evaluation and long-term follow-up. This manuscript summarizes discussions arising from a recent National Institutes of Health conference on nucleic acid therapy, with a focus on scaling technologies for diagnosis of rare disorders and provision of therapies across the age and disease spectrum.