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.
