Designing Preclinical Studies in Germline Gene Editing: Scientific and Ethical Aspects
AbstractHuman germline gene editing is often debated in hypothetical terms: if it were safe and efficient, on what further conditions would it then be ethically acceptable? This paper takes another course. The key question is: how can scientists reduce uncertainty about safety and efficiency to a level that may justify initiation of first-time clinical trials? The only way to proceed is by well-designed preclinical studies. However, what kinds of investigation should preclinical studies include and what specific conditions should they satisfy in order to be considered well-designed? It is argued that multispecies and multigenerational animal studies are needed as well as human embryo editing without implantation. In order to be possible to translate to first-time clinical trials, animal studies need to satisfy strict conditions of validity. Moreover, embryo studies intended for translation to first-time clinical trials need to correspond to the animal studies in experimental design (with exception of implantation). Only in this way can uncertainty about risk for harm (safety) and prospect of benefit (efficiency) in first-time clinical trials be reduced to a modest level. If uncertainty is not reduced to such a level, first-time clinical trials in germline gene editing should not be initiated.
Authors: Karimi G, Vard B, Riyahi R, Motlagh ME, Heshmat R, Kelishadi R Abstract This cross-sectional study was conducted among 14,400 Iranian students, aged 7-18 years to determine the association between the frequency of family dinner and mental health. Family dinner frequency, family relationship, life satisfaction (LS), self-perceived health and anxiety were assessed by validated questionnaires. Of 14,274 participants, 50.6% were boys and 71.4% were urban residents, with a mean (SD) age of 12.28 (3.16) years. Family dinner frequency was significantly correlated with LS (boys: β = 0.27, p
In this study we explored the use of a natural compound rubusoside (RUB) as a solubilizer to enhance the solubility of a fluorescence-labeled C6-Ceramide (NBD C6-Ceramide) and to characterize its pharmacokinetics and tissue distribution in an animal model. RUB significantly enhanced the solubility of NBD C6-Ceramide by forming nanomicelles, and efficiently delivered NBD C6-Ceramide in rats by oral and intravenous administration. RUB loaded 1.96% of NBD C6-Ceramide in the nanomicelles and solubilized it to a concentration of 3.6 mg/mL in water. NBD C6-Ceramide in nanomicelles remained stable in aqueous solutions, all...
Publication date: Available online 10 December 2019Source: Prostaglandins &Other Lipid MediatorsAuthor(s): Giorgio Mottola, Evan Werlin, Bian Wu, Mian Chen, Anuran Chatterjee, Melinda Schaller, Michael S. ConteAbstractInflammation ensuing from vascular injury promotes intimal hyperplasia (IH) and restenosis. Resolvin D1 (RvD1) is a lipid mediator that attenuates IH in vivo when delivered locally to the vessel wall in animal models. We tested the hypothesis that peri-procedural oral administration of RvD1 could blunt the local inflammatory response to angioplasty, and attenuate downstream IH. Carotid angioplasty was per...
First-of-its-kind trial evaluates decision aid’s efficacy
Authors: Glauser W PMID: 31818934 [PubMed - in process]
Authors: Owens B PMID: 31818933 [PubMed - in process]
Authors: Dermer M, Martel J, Greenhill A PMID: 31818932 [PubMed - in process]
Authors: Robson R PMID: 31818931 [PubMed - in process]
Authors: Lamb S PMID: 31818930 [PubMed - in process]
Authors: Zimmer V, Glanemann M, Lammert F PMID: 31818929 [PubMed - in process]