RNA Targeting in CNS Therapeutics

While it is well established that point mutations in DNA are the major cause of inherited disease in humans, the effect on RNA appears to be skewed toward deleterious changes in RNA splicing. This appears to be particularly important for central nervous system (CNS) disorders, where recent genomic studies identify global changes in disease-associated transcript variants in brain tissue from patients, which strongly correlates with changes in cis- and trans-acting splicing factors. In this Research Topic, we aim to highlight recent trends in therapeutic successes for targeting defects in human RNA splicing in neurologic disease. Using the paradigm shown for spinal muscular atrophy (SMA), wherein a splicing defect has been corrected using both antisense oligonucleotide therapeutics and gene targeting therapies, the goal is to discuss recent progress in RNA splicing research that can be exploited to accelerate targeted therapies in several major CNS disorders including Alzheimer’s and Parkinson’s disease, as well as ALS and other psychiatric disorders. Here the focus will be on new opportunities to target defective RNA splicing mechanisms with the latest molecular therapeutics approaches including genetic medicines as well as small molecule approaches that target RNA structures and sequences. These approaches have led to innovation in how we treat specific point mutations, and may reveal novel ways to structure personalized therapies in disease. RNA therapeutics represent a disruptive technology for pharmaceutical treatments that can target previously “undruggable” pathways of disease, and the exponential increase in clinical trials using RNA highlights the importance of this emerging medical modality.

This Research Topic can include articles in the area of RNA splicing in neurologic disease, specifically articles that highlight changes in both cis- and trans-acting factors that play a direct role in regulation of splicing, and their implication in CNS disorders. Particular interest in articles around Alzheimer’s and Parkinson’s disease, as well as ALS and other neuropsychiatric disorders including schizophrenia, autism, depression and bi-polar disorders, epilepsy, and neuro-muscular disorders. These may include genomics-based research as well as individual gene and pathway-based research in these areas, as well as articles highlighting new approaches to delivery mechanisms for RNA therapeutics. The types of RNA therapeutics may include small RNAs (miRNAs, oligonucleotides, siRNAs, aptamers) as well as mRNAs. Article types include primary original research articles (as well as brief research report), clinical trials, mini review articles, methods articles, hypothesis and theory articles, perspective articles, and opinion articles.

Topic Editor Dr. Peter Vanderklish is working as Chief Scientific Officer for the company Spinogenix, and Dr. Vince Mauro is working as Chief Scientific Officer and Senior Vice President for the company Promosome.