Combination therapies are the most common type of therapy for the three rare diseases, according to the co-occurrence analysis on data from the CAS Content Collection (Figure ). Current research indicates that drugs acting at a single target may be insufficient for the treatment of multifactorial neurodegenerative diseases such as HD and ALS, typified by the coexistence of multiple etiopathologies including oxidative stress, protein misfolding and aggregation, mitochondrial dysfunction, inflammation, and metal accumulation at the sites of neurodegeneration. Clearly, combination drug therapy of neurodegenerative diseases with multifunctional remedies exhibiting diverse biological properties is supposed to have distinct advantage. ALS and HD frequently co-occur with gene therapy, while for MG, immunotherapy is the second most frequently occurring after combination therapy (Figure ). Indeed, with respect to ALS, over 50 genes have been identified as either cause or modifier in ALS and ALS/frontotemporal dementia spectrum disease. Substantial effort has been made to discover pathways underlying the pathogenesis of these gene mutations. Accordingly, targeting etiologic genes to suppress their toxic impacts have been investigated widely, with the major strategies including: removal or inhibition of abnormally transcribed RNA using miRNA or antisense oligonucleotides (ASOs); degradation of abnormal mRNA using RNA interference (RNAi); decrease or inhibition of mutant proteins by using, e.g., antibodies against misfolded proteins; and/or DNA genome editing with methods such as CRISPR or CRISPR/Cas. The favorable results of these studies have resulted in application of some of these strategies in clinical trials for ALS, especially for C9orf72 and SOD1. Regarding HD, gene therapies are being explored using genetic material to ramp up expression of genes whose functions are declined or are damaged over the course of the disease, to boost the brain and body's natural resilience against disease progression. 368 As a monogenic disease, HD is a good target for gene therapy approaches, including the use of programmable endonucleases. A protocol for HTT gene knockout using a modified Cas9 protein (nickase, Cas9n) has been recently tested with promising results. Regarding MG, immunotherapeutic biologics are emerging as important therapeutic tools. The monoclonal antibody eculizumab has been approved by the US FDA for refractory MG on the basis of a Phase III trial. Another monoclonal antibody, rituximab, is in advanced stage of clinical trials. A selection of newer anti-CD20 antibodies such as ocrelizumab (CAS RN: 637334-45-3), ofatumumab (CAS RN: 679818-59-8), obinutuzumab (CAS RN: 949142-50-1), ublituximab (CAS RN: 1174014-05-1) or inebilizumab (CAS RN: 1299440-37-1) are also being tested. Enhanced availability of new biologics provides targeted immunotherapies and the chance to develop more specific therapies for MG.