Here we discuss the evolution of key concepts in the field as well as the major technologies and the development pipelines of rare disease treatments. We focus our attention on three specific rare diseases to perform a deeper dive into the research outlook in order to identify and understand obscure connections in these topics, namely: (i) amyotrophic lateral sclerosis (ALS), a terminal neurodegenerative disease affecting the central nervous system (CNS) resulting in progressive loss of motor neurons that control voluntary muscles; (ii) Huntington's disease (HD), another terminal neurodegenerative disease that causes progressive degeneration of nerve cells in the brain, with a wide impact on a person's functional abilities; and (iii) myasthenia gravis (MG), a chronic autoimmune synaptopathy leading to skeletal muscle weakness.