The Future of Rare Diseases

What are rare diseases? What challenges exist in the field and what innovations might improve the diagnostic and treatment capabilities? What is the contribution of RNA sequencing? Today for International Rare Disease Day, researchers join Dolev Vakanin’s article where he answers these questions and explains this global issue.

The question of how infrequent rare diseases really are is controversial, and definitions vary around the world: in the United States, a disease that affects fewer than 200,000 people in total (equal to a ratio of 12 patients per 20,000 people) is considered rare, while in Europe the threshold is less than 1 patient per 2,000 people. This incidence can vary in accordance with genetic and ethnic factors. For example, Tay-Sachs disease is defined as a rare disease in the United States, but it is more common among Ashkenazi Jews, so in Israel there are more patients relative to the general population. Due to their low frequency, these diseases are sometimes overlooked and suffer from a lack of attention, which leads to challenges in diagnosis and treatment, underscoring the need for research as well as improved awareness of the subject.

RNA sequencing

It is estimated that 80% of rare diseases have a genetic component, a fact that holds significant potential for breakthroughs in the fields of diagnosis and treatment. One way to cope with the diagnostic challenges is the use of RNA sequencing, a technique that improves diagnostic ability in 15-17% of cases in which classic methods, such as DNA sequencing, fail to diagnose a rare disease, as demonstrated in an article on the subject published in 2022. According to the article, RNA sequencing reveals an additional layer of information by identifying various processes such as abnormal splicing, epigenetic changes, changes in the promoter region, and more. In addition, RNA sequencing makes it possible to detect mono-allelic expression, a situation in which there are 2 different alleles but only one of them is expressed, while the other is silenced, thus creating a basis for the expression of mutations and the development of various diseases.

While the contribution to the diagnosis of rare diseases is indeed significant, it involves various challenges, including detection of cells that express the defective genes. Gene expression changes not only throughout the stages of development of the organism, but between different tissue types as well. For example, heart cells will express genes and proteins that are different from those expressed in nerve cells. Furthermore, study of the cells requires access to them, which can be challenging, such as in the case of brain cells, in contrast to accessible cells such as skin cells. Moreover, these processes involve a huge amount of information and require the use of advanced tools for analysis of the information and generation of significant insights.

Artificial intelligence

Despite the low prevalence of these diseases, the field of artificial intelligence has not overlooked them. In recent years, dozens of articles have been published on the subject, among them a 2023 article that presents the current and future use of artificial intelligence for rare diseases: the accuracy of the ability to make a diagnosis aided by the integration of diverse databases and the use of decision support tools; assistance in the development of personalized treatment by tailoring clinical trials; analysis of genetic data; and more. It seems that in the field of rare diseases as well, artificial intelligence will accelerate the field by improving diagnostic and treatment capabilities, once again demonstrating the revolutionary potential of artificial intelligence.

Gene therapy

Gene therapy is expected to revolutionize the manner in which rare diseases are managed, and to provide better solutions in the future. A phase three study published in the New England Journal of Medicine in 2022 demonstrated the therapeutic potential in a trial that included 23 patients with beta-thalassemia, who depend on routine blood transfusions to cope with their disease. The treatment included maturing hematopoietic stem cells in the laboratory with the help of gene therapy, followed by their return to the body. The results of the study demonstrated that thanks to this innovative treatment, 91% of the participants no longer needed blood transfusions. In addition, we recently told you in a blog article that the FDA has granted approval for two innovative drugs in the field for the rare disease sickle cell anemia. The approval marks an important breakthrough in the field and the future contribution of gene therapy.