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

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.

Artificial intelligence

Recently, reports of soldiers infected with a harmful mold called Fusarium during the fighting in the Gaza Strip have been accumulating in Israeli hospitals. The mold, most species of which are not dangerous to humans, is found mainly in plants and soil, and it seems that the soldiers who were infected with the harmful strain were injured, such that the skin barrier, which is considered one of the most important in the body’s defense systems, was damaged.

Fusarium can cause a wide variety of diseases in humans: from superficial infections such as corneal infections (keratitis) and nail infections (onychomycosis) to diseases such as sinusitis, and even disseminated and severe infections. The main issue in dealing with violent strains of fungi and molds, including Fusarium, is that of prevention – i.e., trying to ensure that seriously ill or injured patients remain in sterile environments and are not accidentally exposed to the fungus. In case of infection, there are several antifungal drugs that should help, as well as surgical treatments, in which the tissue infected with the fungus is removed in order to prevent it from spreading.

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.