U.K becomes the first country to approve the controversial ‘Three Parent baby'.

Courtesy: The Sun

TheHuman Fertilization and Embryology Authority (HFEA) announced on Thursday that it is ready to give licenses to clinics for the controversial ‘Three Parent ‘IVF procedures.

HFEA chair Sally Cheshire called it “historic and important" decision to license the treatment, naming it "a world first". She further added “Today’s historic decision means that parents at very high risk of having a child with a life-threatening mitochondrial disease may soon have the chance of a healthy, genetically-related child. This is life-changing for those families. We feel now is the right time to carefully introduce this new treatment in the limited circumstances recommended by the panel.”

courtesy: You Tube 

In response to lobbying by MuscularDystrophy UK, lawmakers voted in favor of this pioneering technique in February, 2015 allowing the use of  DNA from three people to prevent children being born with certain fatal genetic diseases.

The first child born with this technique is expected to take birth at the end of 2017.

The procedure has been developed by scientists at Newcastle University.

Advocates of the new procedure say around 2,500 women could benefit from mitochondrial donation in Britain, equating to around 150 births a year as one in 200 children born in the UK have some form of mitochondrial disorder.

Prof Doug Turnbull, Professor of Neurology and director of the Wellcome Centre for Mitochondrial Research Newcastle University plans to treat 25 carefully selected patients each year.

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. 

 

Image courtesy:The telegraph

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

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."

 These techniques have been referred to with several terms, including "mitochondria replacement," "mitochondrial manipulation," "oocyte modification," "three-person embryos," "three-parent babies," and "nuclear genome transfer" (the most technically accurate).

The procedure can be carried out in one of the two ways.
1) maternal spindle transfer (MST).
2) pronuclear transfer (PNT).

2-ways of the three-parent in vitro fertilization

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 the mother’s healthy nuclear DNA, or 99.8% of her genes, plus the donor’s healthy mitochondria. This egg is then fertilised with the father’s sperm and the embryo is implanted into the woman like any other IVF embryo.

The second procedure is very similar. In pronuclear transfer (PNT), both mother and donor eggs are fertilised with the father’s sperm. Before the eggs have time to split into early-stage embryos, the chromosomes inside them are removed. Those from the donor egg are discarded, and replaced with the chromosomes from the mother’s egg. The resulting egg is fertilised and ready to grow into an embryo in the mother’s womb.

Robert Meadowcroft, CEO of Muscular Dystrophy UK, responds: “Today, this historic decision will open the door to the first licensed treatments being offered to eligible women affected by mitochondrial disease. 

Families have, understandably, had to wait through years of thorough ethical, safety and public reviews. We know of many women who have faced heartache and tragedy, and the sorrow of stillbirths, while trying to start their own family, and this decision gives them new hope and choice for the first time.”

However, many have opposed the approval of the 3-parent baby.  Christian bioethics campaigner James Mildred said: "This is a dangerous step in completely the wrong direction." Another critic commented that it brings us a step closer to designer babies.

SOURCES:

The mirror,UK

Human Fertilisation and Embryology Authority (HFEA)

The Guardian

British Fertility Society

Muscular Dystrophy UK

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

Three parent babies

credits:geneticliteracyproject.com

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

Three parent babies have caught much attention in the year 2015 and Britain’s first such baby will be born as early as 2016.

The procedure has been developed by scientists at Newcastle University.

Advocates of the new procedure say around 2,500 women could benefit from mitochondrial donation in Britain, equating to around 150 births a year as one in 200 children born in the UK have some form of mitochondrial disorder.

Prof Doug Turnbull, Professor of Neurology, Newcastle University, said: “This is very good news for patients with mitochondrial DNA disease and an important step in the prevention of transmission of serious mitochondrial disease".

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."
 These techniques have been referred to with several terms, including "mitochondria replacement," "mitochondrial manipulation," "oocyte modification," "three-person embryos," "three-parent babies," and "nuclear genome transfer" (the most technically accurate).

Photo courtesy- The telegraph

The disease primarily affects children, but adult onset is becoming more and more common.
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.

Depending on which cells are affected, symptoms may include loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infectio.

It takes about 3000 genes to make a mitochondrion.  Mitochondrial DNA encodes just 37 of these genes; the remaining genes are encoded in the cell nucleus and the resultant proteins are transported to the mitochondria.  Only about 3% of the genes necessary to make a mitochondrion (100 of the 3000) are allocated for making ATP.  More than 95% (2900 of 3000) are involved with other functions tied to the specialized duties of the differentiated cell in which it resides.

The procedure can be carried out in one of the two ways.
1) maternal spindle transfer (MST).
2) pronuclear transfer (PNT).

Credits: The Guardian

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 fertilised with the father’s sperm and the embryo is implanted into the woman like any other IVF embryo.

The second procedure is very similar. In pronuclear transfer (PNT), both mother and donor eggs are fertilised with the father’s sperm. Before the eggs have time to split into early-stage embryos, the chromosomes inside them are removed. Those from the donor egg are discarded, and replaced with the chromosomes from the mother’s egg. The resulting egg is fertilised and ready to grow into an embryo in the mother’s womb.

Critics of three-person IVF called this techniques as Slippery slope toward “designer babies " because of  the potential for in vitro fertilized eggs that are genetically engineered to have, for example, blonde hair, more intelligence, more increased athleticism.

Crediits: Teracatu wordpress.com

Little is known about the legal, psychological, and social ramifications for the child of three genetic parents.
Other Experts however, aren't convinced the leap from mitochondrial transfer to genetic trait modification is so direct.

Meanwhile, at the Salk Institute for Biological Studies in La Jolla, California, scientist have developed a gene-editing technique that may prevent mutated mtDNA from being passed down from mother to child.

This technique has been shown to be a success in animals it works by using DNA-cutting enzymes to delete mutated mtDNA, leaving healthy mitochondria intact. By reducing the amount of faulty mtDNA, it aims to restore the balance in favour of healthy mitochondria, reducing the amount of faulty mtDNA passed down to offspring to the point where it does not result in disease.

Debate among British and American scientists has just started.

References:

1. http://www.telegraph.co.uk/news/science/science-news/11386151/Three-parent-babies-the-arguments-for-and-against.html
2. http://www.popsci.com/uk-one-step-closer-using-dna-3-people-make-babies
3. http://www.theguardian.com/science/2015/feb/02/three-parent-babies-explained
4. https://www.geneticliteracyproject.org/2015/06/02/three-parent-babies-parent-3s-impact-may-go-beyond-mitochondria/
5. Britain is on the brink of a perilous vote for 'three-person in vitro fertilization', Marcy Darnovsky and Jessica Cussins, Los Angeles Times, February 8, 2015
6. Marcy Darnovsky, The New York Times, February 23, 2014