Publications by authors named "Chris MacLauchlin"
Oligonucleotide therapeutics (ONTs) encompass classes of medicines that selectively target and potentially ameliorate previously untreatable and often rare diseases. Several unique classes of ONTs provide versatility, enabling direct modulation of gene expression by virtue of Watson-Crick base pairing or modulation of cell signaling through structural mimicry or interference with protein-receptor interactions. Due to a lack of suitable in vitro models capable of recapitulating or predicting in vivo effects of ONTs, their discovery and optimization has relied heavily on animal studies for predicting efficacy and safety in humans.
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- GalNAc ligands are critical for the targeted delivery of oligonucleotide therapeutics like siRNAs to liver cells, leading to successful treatments such as GIVLAARI, OXLUMO, and Leqvio.
- Despite progress, there's limited published data on the drug metabolism and pharmacokinetic properties of GalNAc-siRNA, prompting a review to summarize current understanding.
- Research shows that GalNAc-conjugated siRNAs rapidly distribute to the liver post-injection, with liver pharmacokinetics being better indicators of drug effectiveness than blood levels, and these properties are consistent and predictable across different species.
Purpose: Macrolide antibiotics are commonly prescribed treatments for drug-resistant bacterial infections; however, many macrolides have been shown to cause liver enzyme elevations and one macrolide, telithromycin, has been pulled from the market by its provider due to liver toxicity. This work seeks to assess the mechanisms responsible for the toxicity of macrolide antibiotics.
Methods: Five macrolides were assessed in in vitro systems designed to test for bile acid transporter inhibition, mitochondrial dysfunction, and oxidative stress.
Background: Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described.
Methods: In a phase 2 open-label randomized study, we evaluated oral FA/RIF vs standard-of-care (SOC) intravenous antibiotics for treatment of hip or knee PJI.