Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of ELX‐02, a Potential Treatment for Genetic Disorders Caused by Nonsense Mutations, in Healthy Volunteers
Sign Up to like & getrecommendations! Published in 2019 at "Clinical Pharmacology in Drug Development"
DOI: 10.1002/cpdd.647
Abstract: ELX‐02 is an investigational synthetic eukaryotic ribosome–selective glycoside optimized as a translational read‐through molecule that induces read through of nonsense mutations, resulting in normally localized full‐length functional proteins. ELX‐02 is being developed as a therapy… read more here.
Keywords: caused nonsense; safety; increase; single ascending ... See more keywords
Resorting the function of the colorectal cancer gatekeeper adenomatous polyposis coli
Sign Up to like & getrecommendations! Published in 2019 at "International Journal of Cancer"
DOI: 10.1002/ijc.32557
Abstract: As a large number of cancers are caused by nonsense mutations in key genes, read‐through of these mutations to restore full‐length protein expression is a potential therapeutic strategy. Mutations in the adenomatous polyposis coli (APC)… read more here.
Keywords: polyposis coli; number; nonsense mutations; polyposis ... See more keywords
New Negamycin-Based Potent Readthrough Derivative Effective against TGA-Type Nonsense Mutations.
Sign Up to like & getrecommendations! Published in 2019 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.9b00273
Abstract: We report a novel negamycin derivative TCP-1109 (13x) which serves as a potent readthrough drug candidate against nonsense-associated diseases. We previously demonstrated that TCP-112 (7), a nor-compound of native 3-epi-deoxynegmaycin, showed a higher readthrough activity… read more here.
Keywords: tga; compound; potent readthrough; nonsense mutations ... See more keywords
2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations
Sign Up to like & getrecommendations! Published in 2020 at "Nature Communications"
DOI: 10.1038/s41467-020-15140-z
Abstract: Nonsense mutations cause about 10% of genetic disease cases, and no treatments are available. Nonsense mutations can be corrected by molecules with nonsense mutation readthrough activity. An extract of the mushroom Lepista inversa has recently… read more here.
Keywords: highly potent; diaminopurine highly; nonsense mutation; nonsense mutations ... See more keywords
First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis.
Sign Up to like & getrecommendations! Published in 2019 at "Clinical science"
DOI: 10.1042/cs20180676
Abstract: Recently, a novel heterozygous missense mutation c.T1421G (p. L474R) in the PODXL gene encoding podocalyxin was identified in an autosomal dominant focal segmental glomerulosclerosis (AD-FSGS) pedigree. However, this PODXL mutation appeared not to impair podocalyxin… read more here.
Keywords: podxl nonsense; nonsense mutations; dominant focal; autosomal dominant ... See more keywords
ELX-02: an investigational read-through agent for the treatment of nonsense mutation-related genetic disease
Sign Up to like & getrecommendations! Published in 2020 at "Expert Opinion on Investigational Drugs"
DOI: 10.1080/13543784.2020.1828862
Abstract: ABSTRACT Introduction ELX-02, an investigational compound that is structurally an aminoglycoside analog, induces read-through of nonsense mutations through interaction with the ribosome, through which full-length functional proteins can be produced. It is being developed as… read more here.
Keywords: treatment; elx investigational; disease; read agent ... See more keywords
Translational readthrough of GLA nonsense mutations suggests dominant-negative effects exerted by the interaction of wild-type and missense variants
Sign Up to like & getrecommendations! Published in 2019 at "RNA Biology"
DOI: 10.1080/15476286.2019.1676115
Abstract: ABSTRACT Nonsense mutations are relatively frequent in the rare X-linked lysosomal α-galactosidase A (α-Gal) deficiency (Fabry disease; FD), but have been poorly investigated. Here, we evaluated the responsiveness of a wide panel (n = 14)… read more here.
Keywords: missense variants; dominant negative; interaction wild; nonsense mutations ... See more keywords
Nonsynonymous, synonymous and nonsense mutations in human cancer-related genes undergo stronger purifying selections than expectation
Sign Up to like & getrecommendations! Published in 2019 at "BMC Cancer"
DOI: 10.1186/s12885-019-5572-x
Abstract: BackgroundNonsynonymous mutations change the protein sequences and are frequently subjected to natural selection. The same goes for nonsense mutations that introduce pre-mature stop codons into CDSs (coding sequences). Synonymous mutations, however, are intuitively thought to… read more here.
Keywords: synonymous nonsense; cancer related; nonsynonymous synonymous; related genes ... See more keywords
Hairless Gene Nonsense Mutations in Alopecia Universalis: A Case Report
Sign Up to like & getrecommendations! Published in 2021 at "Iranian Journal of Public Health"
DOI: 10.18502/ijph.v50i6.6429
Abstract: Alopecia universalis (AU) congenital, known as generalized atrichia, is a severe form of autosomal recessive alopecia that results in complete hair loss of scalp and body. Mutations in the human hairless gene (HR) are associated… read more here.
Keywords: mutations alopecia; gene nonsense; hairless gene; nonsense mutations ... See more keywords
Targeted pseudouridylation: An approach for suppressing nonsense mutations in disease genes.
Sign Up to like & getrecommendations! Published in 2023 at "Molecular cell"
DOI: 10.2139/ssrn.3988395
Abstract: Nonsense mutations create premature termination codons (PTCs), activating the nonsense-mediated mRNA decay (NMD) pathway to degrade most PTC-containing mRNAs. The undegraded mRNA is translated, but translation terminates at the PTC, leading to no production of… read more here.
Keywords: pseudouridylation approach; pseudouridylation; nonsense mutations; suppression ... See more keywords
Readthrough of SCN5A Nonsense Mutations p.R1623X and p.S1812X Questions Gene-therapy in Brugada Syndrome.
Sign Up to like & getrecommendations! Published in 2017 at "Current gene therapy"
DOI: 10.2174/1566523217666170529074758
Abstract: PURPOSE Nonsense mutation readthrough is used as a gene-specific treatment in some genetic diseases. The response to readthrough treatment is determined by the readthrough efficiency of various nonsense mutations. In this manuscript, we aimed to… read more here.
Keywords: sodium; r1623x s1812x; channel; mutations r1623x ... See more keywords