China
Africa
Explore chapters and articles related to this topic
Elevated Cytosolic Phospholipase A2α as a Target for Treatment and Prevention the Progression of Neurodegenerative Diseases
Published in P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas, Advanced Studies in Experimental and Clinical Medicine, 2021
Rachel Levy, Yulia Solomonov, Kesenia Kasianov, Yafa Malada-Edelstein, Nurit Hadad
Inhibition of cPLA2α upregulation in the cortex of Ab brain infusion (a mouse model of AD) as shown in our previous study [8] prevented the behavioral deficit. Similarly, inhibition of cPLA2α upregulation in the spinal cord of hmSOD1 mice (a mouse model of ALS) at the onset of the disease symptoms [9] significantly delayed the development of the disease. Increased expression and activity of cPLA2α have been detected in all cell types in the spinal cord, brainstem, and cortex of both sporadic and familial ALS, suggesting that cPLA2α may have an important role in the pathogenesis of the disease in all ALS patients. The antisense treatment that reduced cPLA2α upregulation in the brain and/or the spinal cord of antisense treated mice, prevented the reduction in the number of neurons (detected by NeuN), inhibited astrocyte activation (detected by GFAP) and microglial activation (detected by Iba-1 and/or by CD40). In addition, antisense treatment blunted the upregulation of the pro-inflammatory enzymes: inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The activation of microglia detected by CD40 overexpression is regulated by cPLA2α. In conclusion, antisense drug treatment is an exciting and emerging specialty area, not as yet in common use. Various antisense drugs for a variety of diseases and disorders are now in clinical phase testing, evincing the potential and promise of antisense drugs as a treatment strategy.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
When expression of a particular gene is the cause of a disease such as cancer, and the sequence of the gene is known, the antisense therapy approach involves the use of a strand of nucleic acid (DNA, RNA, or a chemical analog of either) to target the messenger RNA (mRNA) produced by that gene to inactivate it and turn the gene “off”. Various strategies include targeting the promoter or coding regions of genes, the splicing sites on pre-RNA, or modifications of the exons of mRNA segments.
A Brief History of Genetic Therapy: Gene Therapy, Antisense Technology, and Genomics
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
The diverse observations which have been made in a basic research vein have raised issues in some quarters with respect to the rate or manner in which an antisense approach to therapeutic development should be pursued. Some of these issues arise from fundamentally different perspectives regarding the application of antisense technology. From a basic research perspective, there is a tremendous desire to understand many of the parameters surrounding antisense activity. These include cellular uptake, site and mechanism of oligonucleotide action. There is also a desire on the part of basic researchers to fully interpret every phenomenon which is found in association with antisense activity-to understand the whole story before advancing the application of the technology. In this regard, some have sounded a cautionary note with regard to antisense therapeutic development (Stein and Cheng, 1993).
Investigational new drugs for the treatment of Dravet syndrome: an update
Published in Expert Opinion on Investigational Drugs, 2023
Slobodan M. Janković, Snežana V. Janković, Radiša Vojinović, Snežana Lukić
For the further progress of disease-modifying therapy of Dravet syndrome, it is crucial to improve the technology of introducing DNA fragments or whole genes into the central nervous system and especially the target cells. For now, mostly adenoviruses and adeno-associated virus serotype 9 are used as vectors for this purpose, but their capacity in terms of the size of the genes they can accommodate is limited, which limits the direct use of larger genes, such as SCN1A. In addition, it is necessary to take a better look at the possible side effects of disease modifying therapy, given that clinical studies of rare diseases such as Dravet syndrome cannot include a large number of patients. When using antisense oligonucleotides, two types of side effects are possible, hybridization-dependent and hybridization-independent [42], while in gene therapy, side effects can be the result of insertional mutagenesis or immune reaction [43]. That is why it is necessary to include every patient with Dravet syndrome, who in the future will receive some of the disease-modifying drugs outside of clinical studies, in a well-organized prescription event monitoring program.
Antisense Oligonucleotide Therapy for Ophthalmic Conditions
Published in Seminars in Ophthalmology, 2021
Kevin Ferenchak, Iris Deitch, Rachel Huckfeldt
Antisense oligonucleotides are synthetic single-stranded fragments of nucleic acids that bind to a specific complementary messenger RNA (mRNA) sequence, modify translation, and change the final gene product. AON thus alter gene expression before a pathogenic protein is made. Given their targeted mechanism of action, they have been a focus of research for clinical application since they were first described as possible therapeutic agents in 1978 by Zamecnik and Stephenson.3 As discussed further below, the first FDA–approved AON was for the treatment of cytomegalovirus (CMV) retinitis. Fewer than ten modern AON have now been approved by the by the United States Food and Drug Administration (FDA), mostly for treating Mendelian diseases with recently approved examples including skipping exon 51 in the DMD gene causing Duchenne muscular dystrophy with intravenous eteplirsen, and splicing modification of the SMN2 gene into a functional SMN1 gene for spinal muscular atrophy with intrathecal nusinersen.4–6 AON are a similarly attractive therapy for inherited retinal disorders (IRDs), and recent papers have reviewed the proof-of-concept studies of AON for these conditions.7,8
Resolution of coronavirus disease 2019 (COVID-19)
Published in Expert Review of Anti-infective Therapy, 2020
Khaled Habas, Chioma Nganwuchu, Fanila Shahzad, Rajendran Gopalan, Mainul Haque, Sayeeda Rahman, Anwarul Azim Majumder, Talat Nasim
Antisense RNA therapies including antisense oligonucleotides (ASOs), small RNAs or long non-coding RNAs have been considered to specifically treat various disorders including viral diseases. Upon entering the ASOs inside the host cells, they bind to the RNA target, resulting the formation of double-stranded hetero-duplex, which is then cleaved by cellular RNase H1 [71] . Formivirsen (Vitravene) is the first FDA-approved ASO, which inhibits the expression of major immediate early region 2 of the cytomegalovirus [72]. The drug has been approved for the treatment of peripheral cytomegalovirus retinitis in patients with AIDS [73]. Antisense RNAs have been used in clinical trials in various disorders including cancers, myopathies and Huntington’s disease [74]. As antisense-based therapies have shown beneficial effects in other diseases and they are easy to design and cost-effective to manufacture compared with small molecules and antibodies, they may hold promise for rapid drug development for SARS-CoV infections [75].