Friday, September 30, 2016

First healthy ‘Three parent baby ‘born in US after spindle nuclear transfer.

A healthy baby boy was born on April 6 to a mother whose two children have died previously at age of 8months and 6 years due to Leigh syndrome. She also had history of four spontaneous abortions.

Leigh syndrome is a debilitating disease with damage is to the basal ganglia and brainstem. Symptoms are the fatigue and weakness typical of mitochondrial diseases, plus double vision, drooping eyelids, trouble swallowing, dystonia of the upper arms, and gradual motor deterioration.

The cause of this syndrome is single-base mutation in a mitochondrial gene that encodes subunit 6 of the ATPase gene. The newborn's mother carries that mutation. 

Mutations in mitochondrial DNA are maternally inherited and are responsible for causing many debilitating disorders without definitive treatment. Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems.

Mitochondrial replacement therapy, has been shown to be a novel technology in minimizing mutated mtDNA transmission from oocytes to pre-implantation embryos.

This past February, after a yearlong debate the United Kingdom became the first [1]country to legalize mitochondrial replacement therapy (MRT), also known as mitochondrial DNA replacement, which can be used to make “three-parent babies.”

The procedure is still controversial in US, US FDA ascertaining in 2015 that more data is needed before legalizing the procedure while Institute of Medicine concluding in 2016 that it can be allowed under limited condition.

In this technique the nucleus of an affected woman's extracted egg is removed and is put into the enucleated egg of another woman, which contains her mitochondria. The child would thus be genetically related to three people, which is why the media often refers to "three-parent babies" or "three-parent in vitro fertilization."

 The procedure can be carried out in one of the two ways.
1) Spindle Nuclear Transfer(SNT).
2) pronuclear transfer (PNT).

The simpler of the two is called maternal spindle transfer (MST). First, doctors use standard IVF treatment to collect eggs from the mother. They then remove the nucleus from one of the mother’s eggs and transfer it into a healthy donor egg that has had its own nucleus removed. The reconstituted egg holds all of the mother’s healthy nuclear DNA, or 99.8% of her genes, plus the donor’s healthy mitochondria. This egg is then fertilized with the father’s sperm and the embryo is implanted into the woman like any other IVF embryo.

John Zhang, MD, PhD performed the procedure in Mexico to avoid legal issues. The paper is published in current issue of Fertility and Sterility.[2] In this case, the mother carried the mutation with 24.5% mtDNA displaying the altered gene. Due to religious reasons the parents opted for Spindle Nuclear Transfer(SNT).  

Five metaphase II oocytes were subjected to meiotic SNT and fertilized by ICSI.  Four of the embryos developed into blastocysts, PGS showed that one blastocyst was euploid (46XY), while the rest were aneuploidy. The single euploid was transferred which resulted in an uneventful pregnancy.

Only 2% of baby’s mitochondria had mother’s mutation.The baby is currently 3 months old and is very healthy.



[1] http://www.popsci.com/3-parent-babies-are-now-legal-united-kingdom
[2] http://www.fertstert.org/article/S0015-0282(16)62670-5/fulltext

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