Antisense Oligonucleotide (ASO)-depends Neurological Disease Solutions
Antisense oligonucleotides (ASOs) represent a new and highly promising class of drugs for personalized medicine. They may finally provide a therapeutic platform for developing drugs for the treatment of severe neurodegenerative and neurological diseases. Creative Biolabs focuses on neuroscience research and can provide a one-stop service for ASO research to promote your project quickly.
Overview of ASO Drug
ASO drugs are an emerging class of therapeutics designed to alter RNA expression and function, thus allowing the possibility for therapeutic intervention beyond protein or receptor engagement. Recently ASO drugs have demonstrated progress to treat diseases of the central nervous system (CNS). ASOs are currently being investigated pre-clinically for many CNS diseases using a variety of targets and mechanisms.
Mechanism of ASO Therapies
ASOs can modulate RNA in many different ways. The most commonly utilized mechanism is that of RNA degradation or “knockdown”, which results in the selective reduction of the RNA and, if applicable, the downstream protein of interest. This mechanism recruits endogenous RNase H into the ASO/RNA complex and requires an unmodified fragment of DNA in the middle of the ASO molecule to provide a substrate for RNase H binding. Another typical ASO mechanism is "splice modification", where fully modified ASOs for pre-mRNA switches between different splice isoforms by exon skipping. Importantly, ASOs can target RNA in the nucleus and/or in the cytoplasm and are capable of modulating many forms of RNA.
Fig.1 Schematic description of several mechanisms of action of synthetic ASO. (Wurster, 2018)
Antisense Oligonucleotides in Neurological Disorders
Given the good underlying pathogenesis of ASOs and mutations in single or only a few genes, the potential efficacy of ASOs for the following diseases is credible.
Spinal muscular atrophy (SMA) is a genetic autosomal-recessive disease. There is an antisense drug that binds to a site in intron 7 of the SMN2 pre-mRNA, displacing hnRNPA1/A2 proteins which negatively regulate splicing of exon 7, resulting in full length SMN2 transcripts, which has been approved for the treatment of SMA in more than 40 different countries.
Amyotrophic lateral sclerosis is a severe neurodegenerative disease. Targeting SOD1 as a potential treatment for ALS is the first time ASOs have been used to treat neurodegenerative diseases. The second target of ASO for the treatment of sporadic ALS is RNA encoding the RNA-binding protein ataxin-2.
Two therapeutic targets heavily researched as potential therapies for Alzheimer’s disease are amyloid precursor protein (APP) and tau. ASO can be used to block tau synthesis or to synthesize a potentially less pathogenic form of tau by selective RNA splicing and is being explored as a potential therapeutic approach.
Alpha-synuclein is thought to be an underlying driver of PD. The suppression of alpha-synuclein with ASOs has disease-modifying benefits in multiple models. ASOs may be a transformative disease modification therapy for PD.
Creative Biolabs is the premier neuroscience research CRO company in the United States. ASOs regulate the cause and pathway of disease through a unique set of mechanisms and are an exciting alternative to the treatment of diseases of the CNS. You can completely rely on our skilled scientists to provide you with tailor-made solutions to make your ASO research easier. Please feel free to contact us for more detail.
- Wurster, C.D.; Ludolph, A.C. Antisense oligonucleotides in neurological disorders. Therapeutic advances in neurological disorders. 2018, 11: 1756286418776932.