From the lab to the people: major challenges in the biological treatment of Down syndrome

Abstract

Down syndrome (DS) refers to a genetic condition due to the triplication of human chromosome 21. It is the most frequent autosomal trisomy. In recent years, experimental work has been conducted with the aim of removing or silencing the extra chromosome 21 (C21) in cells and normalizing genetic expression. This paper examines the feasibility of the move from laboratory studies to biologically treating “bone and flesh” people with DS. A chromosome or a gene therapy for humans is fraught with practical and ethical difficulties. To prevent DS completely, genome editing would have to be performed early on embryos in the womb. New in vitro findings point toward the possibility of epigenetic silencing the extra C21 in later embryonic or fetal life, or even postnatally for some aspects of neurogenesis. These possibilities are far beyond what is possible or allowed today. Another approach is through epigenetic regulation of the overexpression of particular genes in C21. Research with mouse modeling of DS is yielding promising results. Human applications have barely begun and are questioned on ethical grounds.

Gene Expression Studies in Down Syndrome; What Do They Tell Us about Disease Phenotypes?

“…The practicalities of utilising gene silencing is currently difficult due to having to confirm T21 very early on and then successfully delivering gene therapy before phenotypical features begin to develop. Rondal highlights that to normalize embryonic development ideally gene therapy would be implicated day 3 post insemination, as the cells are multipotent [67]. As mentioned about there is also a lot of ethical debate surrounding this topic, in 2014 Inglis et al, produced a questionnaire to allow for parents to have their opinions on whether they would want gene therapy [62].…”