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.