Therapies for rare diseases: therapeutic modalities, progress and challenges ahead.,Nature Reviews Drug Discovery

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Therapies for rare diseases: therapeutic modalities, progress and challenges ahead.
Nature Reviews Drug Discovery ( IF 122.7 ) Pub Date : 2019-12-13 , DOI: 10.1038/s41573-019-0049-9
Erik Tambuyzer _{1,

2} , Benjamin Vandendriessche _{3,

4} , Christopher P Austin ₅ , Philip J Brooks ₅ , Kristina Larsson ₆ , Katherine I Miller Needleman ₇ , James Valentine ₈ , Kay Davies ₉ , Stephen C Groft ₅ , Robert Preti ₁₀ , Tudor I Oprea _{11,

12} , Marco Prunotto ₁₃

Affiliation

BioPontis Alliance for Rare Diseases Foundation fup/son, Brussels, Belgium.
BioPontis Alliance Rare Disease Foundation, Inc, Raleigh, NC, USA.
Byteflies, Antwerp, Belgium.
Department of Electrical, Computer, and Systems Engineering (ECSE), Case Western Reserve University, Cleveland, OH, USA.
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
Orphan Medicines Office, European Medicines Agency, Amsterdam, Netherlands.
Office of Orphan Products Development, Food and Drug Administration, Silver Spring, MD, USA.
Hyman, Phelps & McNamara, Washington, DC, USA.
MDUK Oxford Neuromuscular Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Hitachi Chemical Regenerative Medicine Business Sector, Allendale, NJ, USA.
Translational Informatics Division, Department of Internal Medicine, University of New Mexico Albuquerque, Albuquerque, NM, USA.
UNM Comprehensive Cancer Center, University of New Mexico Health Science Center, Albuquerque, NM, USA.
School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.

Most rare diseases still lack approved treatments despite major advances in research providing the tools to understand their molecular basis, as well as legislation providing regulatory and economic incentives to catalyse the development of specific therapies. Addressing this translational gap is a multifaceted challenge, for which a key aspect is the selection of the optimal therapeutic modality for translating advances in rare disease knowledge into potential medicines, known as orphan drugs. With this in mind, we discuss here the technological basis and rare disease applicability of the main therapeutic modalities, including small molecules, monoclonal antibodies, protein replacement therapies, oligonucleotides and gene and cell therapies, as well as drug repurposing. For each modality, we consider its strengths and limitations as a platform for rare disease therapy development and describe clinical progress so far in developing drugs based on it. We also discuss selected overarching topics in the development of therapies for rare diseases, such as approval statistics, engagement of patients in the process, regulatory pathways and digital tools.

中文翻译：

罕见病治疗：治疗方式、进展和未来挑战。

尽管研究取得了重大进展，提供了了解其分子基础的工具，并且立法提供了监管和经济激励措施以促进特定疗法的发展，但大多数罕见疾病仍然缺乏获得批准的治疗方法。解决这一转化差距是一个多方面的挑战，其中一个关键方面是选择最佳治疗方式，将罕见病知识的进步转化为潜在的药物，即孤儿药。考虑到这一点，我们在此讨论主要治疗方式的技术基础和罕见病适用性，包括小分子、单克隆抗体、蛋白质替代疗法、寡核苷酸和基因和细胞疗法，以及药物再利用。对于每种模式，我们认为其作为罕见病治疗开发平台的优势和局限性，并描述了迄今为止开发基于它的药物的临床进展。我们还讨论了罕见疾病疗法开发中的选定总体主题，例如批准统计、患者参与过程、监管途径和数字工具。

更新日期：2019-12-17

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