China
Africa
Explore chapters and articles related to this topic
Polynuclear Platinum Drugs
Published in Astrid Sigel, Helmut Sigel, Metal Ions in Biological Systems, 2004
The study of platinum compounds in antisense and antigene applications has been pioneered by Leng and Lippert [83,84]. The high charge and high affinity for DNA of polynuclear platinum compounds suggest the possibility of improving delivery and enhancing nuclease resistance of antisense oligodeoxynucleotides through complexation [85]. Two methodologies can be considered – DNA neutralisation through non-covalent binding to the oligodeoxynucleotide through electrostatic and hydrogen bonding interactions or covalent attachment of the molecule to the oligodeoxynucleotide (Figure 9). Reduced negative charge of the antisense oligodeoxynucleotide can facilitate cellular uptake. The high affinity binding of the compound to the oligodeoxynucleotide may further protect the complex from cellular nucleases capable of degrading the antisense oligodeoxynucleotide – in this aspect there is a formal analogy to inhibition of other DNA-processing activity such as polymerase and transcription by bulky lesions.
Advances in autoimmune myasthenia gravis management
Published in Expert Review of Neurotherapeutics, 2018
Shuhui Wang, Iva Breskovska, Shreya Gandhy, Anna Rostedt Punga, Jeffery T. Guptill, Henry J. Kaminski
The oldest effective treatment for MG is inhibition of ChE. No fundamental change in this approach has occurred in over eight decades. A potentially promising treatment was assessed in Phase-1b open-label trial with oral EN101 with patient reported and objective measures showing improvement [159]. Additionally, improvement was maintained for greater than 24 h, which would be a great improvement over pyridostigmine. EN101 is an antisense oligodeoxynucleotide that acts at the mRNA level and selectively reduces the enzymatic isoform of AChE-R, which is generated with injury to the NMJ produced by MG [160,161]. Despite its promise no commercial interests have moved development forward. There is some interest in improving pyridostigmine by limiting its adverse effect profile or improving the pharmacokinetic profile, but none have moved to phase-2 development. Also, a potassium channel inhibitor, amifampridine phosphate, is under phase-3 evaluation. The agent appears to improve acetylcholine release and muscle contraction. Tirasemtiv is a troponin activator, which enhances the force generation of muscle contraction, is in phase-2 assessment. The question is whether these latter two compounds will be significant improvements compared to cholinesterase inhibitors.
Recent innovations with drugs in clinical trials for neurotrophic keratitis and refractory corneal ulcers
Published in Expert Opinion on Investigational Drugs, 2019
Dominique Bremond-Gignac, Alejandra Daruich, Matthieu P Robert, Frederic Chiambaretta
CODA001 is an antisense oligonucleotide that downregulates the expression of the gap junction protein Cx43 which is increased in PEDs. The first use in patients with PEDs was reported by Ormonde et al. [18] Five eyes with severe ocular surface burns, which were unresponsive to established therapy, were treated by connexin43-specific antisense oligodeoxynucleotide delivered in cold, thermoreversible Poloxamer407 gel under either amniotic membrane graft or bandage contact lens. The treatment reduced inflammation within 1–2 days, and complete corneal reepithelialization was obtained in all eyes. To date, there is no ongoing clinical trial evaluating CODA001 for corneal ulcers.
c-MYB and DMTF1 in Cancer
Published in Cancer Investigation, 2019
Elizabeth A. Fry, Kazushi Inoue
For the past decades, scientists have been engaged in the development of antisense oligodeoxynucleotide (AS-ODN) drugs that might be more effective for the treatment of leukemias and other human malignancies. c-MYB, c-MYC, and BCR/ABL genes have been chosen since they are often overexpressed in human malignancies and have short half-life mRNAs/proteins.