February 28, 2021 marks the 14^thannual celebration ofInternational Rare Disease Day, the one day a year when we raise awareness of and honor the more than 300 million people worldwide living with a rare disease. This Rare Disease Day, we also suggest taking time to recognize the many advances in biomedical research that people living with rare diseases have contributed, and the benefits this research has brought to the lives of all people throughout the world living with both rare and common diseases.

当我们能够专注于干预较小富集人群的目标时，人们期望有更好的功效和副作用更少

大多数罕见的疾病是单基因（单基因）疾病，其中一个人的DNA发生了很小的变化，通常只有一个基因中的一个碱基对，足以破坏基本的生理过程。罕见的疾病通常代表与典型的细胞功能的偏差，否则在正常工作时可能会忽略或没有研究，并可能导致重要的生物学见解和疗法。例如，早期观察到罕见出血性疾病（例如血友病），我们对凝血级联反应的理解和其他导致毒品的发现和其他方法促进和防止血液凝结的方法的理解，使医疗和外科护理的许多领域受益for some of the world’s most common diseases. Research into the “ultra-rare” disease homozygous familial hypercholesterolemia led to the discovery of cholesterol metabolism, resulting in some commonly prescribed medications for the treatment and prevention of cardiovascular disease. Similar discoveries have been seen for rare diseases where muscles don’t contract, nerves don’t communicate, proteins and carbohydrates aren’t broken down, and the retina fails – all illuminated through rare genetic disorders when usual biological “housekeeping” pathways don’t function as they are supposed to.

罕见的疾病发现也经常是首先 - 第一个化学疗法是罕见的血液癌非霍奇金的淋巴瘤和儿童急性急性淋巴细胞白血病。生物标志物（生物标志物）首次用于监测和治疗癌症是罕见的妊娠子宫癌绒毛膜瘤。最近，迄今为止批准的所有第一个基因疗法都是用于罕见的遗传疾病和罕见的癌症，这些方法现在正在利用更常见的疾病，例如帕金森氏病。精确医学的科学也是概念上一种罕见的疾病方法，现在适应了更常见的疾病。当我们能够专注于干预较小的富集人群的目标时，人们期望有更好的功效和对接受治疗的人的副作用更少，这是我们想要的所有患者的一种方法。

When we are asked why we commit research to rare diseases when there are so few people affected with an individual disease (and we are frequently asked this), the answer is very plain – we study rare because, in addition to the much-needed advances for people with rare diseases, they contribute knowledge and understanding disproportionate to the numbers of patients affected.

NCATS has long recognized the value of rare and has committed substantial resources toward innovative research programs that include research networks, team science, patient and advocate involvement, and research-investigator support and education to expedite therapeutics development and gain efficiencies in the research process. This is exemplified in many NCATS rare disease initiatives, such as the novel “platform” approach for genetic diseases PaVe-GT, where we are working to develop four gene therapies at the same time, ultimately streamlining rare disease gene therapy development and making it more accessible to patients. The Rare Diseases Clinical Research Network is made up of 20 research consortia that are able to collectively study more than 250 different rare diseases. These research teams partner with patients and advocacy groups to better understand disease biology and progression, and develop innovative therapies. Newer programs examine shared molecular etiologies of disease, such as common genetic mutations, for more than one disease within a single study protocol, and focus on diagnostic approaches that combine machine-learning, genomics, and clinical approaches intended to accelerate the often lengthy, years-long rare disease diagnostic odyssey most patients go through to find an accurate diagnosis.

So this Rare Disease Day, if you know one of the estimated 1 in 10 people living with a rare disease, please honor, recognize and – yes – thank them for all they have done and continue to do, to help us to further understand human physiology and accelerate the development of treatments for the thousands of diseases and conditions, common and rare, for which there are still no good therapeutic options.