Live Birth Derived From Oocyte Spindle Transfer to Prevent Mitochondrial Disease

Abstract

(Abstracted from Reprod Biomed 2017;34:361–368) It is estimated that at least 1 in 5000 people in the general population has 1 mutation in mitochondrial DNA (mtDNA), which can cause maternally inherited mitochondrial disorders. When both mutant mitochondrial and wild-type (normal) genomes coexist (heteroplasmy), the severity of symptoms is associated with the level of mtDNA mutation load or degree of heteroplasmy.

Responsible innovation in human germline gene editing: Background document to the recommendations of ESHG and ESHRE

“…These NT technologies appear to be efficient in terms of embryonic development and safe in terms of minimal mtDNA carryover (Yamada et al, 2016;Hyslop et al, 2016). In April 2016, the first child resulting from maternal spindle transfer was born (Zhang et al, 2017).The mother was an asymptomatic carrier of a mitochondrial mutation that caused Leigh syndrome, a fatal neurological disorder. The child, who has 1% of its mother's mtDNA, was healthy at three months, although it is not known if any abnormality might appear later on.…”

Assisted reproductive technologies to prevent human mitochondrial disease transmission

“…Neither fetus had detectable levels of the maternal (karyoplast-derived) mtDNA haplotype. In addition, the use of MST to treat a case of Leigh syndrome has been reported 46 . Transfer of an XY euploid blastocyst following MST resulted in a live birth.…”

“…The sensitivity that surrounds clinical use of MRT was exemplified by the media interest in the UK HFEA's decision to license a clinic to perform MRT (https://www.hfea.gov.uk/about-us/news-and-pressreleases/2017-news-and-press-releases/hfea-statement-on-mitochondrial-donation/) and the birth of a child following treatment in a clinic in Mexico 46 . A number of challenges have been made to MRT on legal and ethical grounds 43,[74][75][76][77] .…”

“…Finally, while in some jurisdictions the clinical use of MRT is unlawful or its regulation non-existent or unclear 43,44 , there have been two reports of the modification of embryos through MRT and their subsequent transfer to women 45,46 . Zhang et al 45 described the use of PNT to establish a pregnancy for a 30-year-old nulligravid woman with unexplained infertility.…”

Understanding Mitochondrial Polymorphisms in Cancer

“…One of the most critical questions is that although whole-genome sequencing of an individual's normal and tumor tissues can decipher what changes have occurred in both mtDNA and nuclear DNA, there is no model system currently available to evaluate the relevance of such changes. How mitochondrial function is altered in the presence of certain combinations of nuclear and mitochondrial genomes remains poorly understood and calls into question the safety of embryonic manipulations, including the three-parent baby (51). Furthermore, evolution may have preselected "compatible" mitochondrial and nuclear genomes to maximize function for survival (49); however, sequencing data argues that as mtDNA haplogroups coexist with divergent nuclear genomes in healthy individuals, "compatibility" is not an issue (16).…”