Baby with three parents?- aka. mitochondrial therapy

February 28, 2014Carole No Comments »

Would anyone read an article about mitochondrial transfer? Not so much. But a screaming headline about human babies that have three parents? – now that gets everyone’s attention. Reality as usual, is more nuanced than the headlines. So before all the hyperventilation starts, let’s get the science part straight.

Mitochondrial DNA. We inherit our mitochondrial DNA in the egg from our mother. Mitochondria are cellular organelles that energize the cells by making energy from the smallest molecules of food we eat. The DNA found in mitochondria does not code for traits like the rest of our DNA and is not housed in the chromosomes. Mitochondria float around in the liquid soup of the cell- the cytoplasm. Because mitochondria are so very critical to energy production at the ATP level, genetic defects in the DNA in these organelles results in hideous diseases that cause suffering and death. Here are a list of diseases with more info.

How is mitochondrial transfer used  in the context of IVF to prevent “inheritance” of mitochondrial disease? –by replacing mutated mitochondrial egg DNA with DNA from a donor who has normal mitochondrial DNA. How do we use mitochondria from egg donors for this procedure? There are two proposed methods. You start with two eggs, one from a patient with the mitochondrial mutation (maternal egg) and one from a healthy donor(donor egg).

At the end of the day, you want to have healthy mitochondrial DNA  form the donor into the same egg with DNA from the couple who want to have a child. There are two recent methods that could be used, pre- or post-fertilization in IVF.

1) Replace mitochondria after fertilization: You can fertilize an the egg using the partner’s sperm in IVF. But now you have a zygote with abnormal mitochondria. How do you fix this? You can empty out a donor egg of the donor chromosomal DNA, leaving only the mitochondrial DNA floating around in the cytoplasm. Next, scoop out the two pronuclei (two circular sacs of membrane enclosing maternal and paternal DNA  from the fertilized egg and move the pronuclei into the emptied  donor egg that only contains healthy donor mitochondria. Now you have the zygote resettled into an egg with healthy donor mitochondria.

2) Replace mitochondria before fertilization. You can prepare an empty egg from the donor by removing the donor nucleus but leave behind the donor mitochondria in an empty egg envelope. Then move the maternal nucleus to the donor egg that is empty of everything but mitochondrial DNA to reconstitute an egg with maternal chromosomal DNA plus donor mitochondria. Then put this “repaired” egg into contact with a sperm for fertilization to occur.

Both these two techniques have been used in animals, including non-human primates. These type of transfers have not yet been used to have children.

However, in 2001, 30 children were born from a similar but simplified procedure in which fluid from a donor egg was removed. The fluid contained a soup of molecules including donor mitochondria plus other proteins and RNAs. This cytoplasmic fluid was then injected into the patient’s eggs with the sperm at the time of sperm injection. Of course, the patient still had their own mitochondria after cytoplasmic transfer so it was not designed as a cure for mitochondrial disease. What was the point of those early experiments more than a decade ago? The purpose of cytoplasmic transfer was to treat infertility due to recurrent implantation failure.  The FDA intervened and stopped these procedures.

Mitochondrial power is the also the concept behind the work of Ovascience which is looking to prepare mitochondrial extracts from egg stem cells to rejuvenate older eggs. In this case, they are not using donor eggs, but using stem cells from the patient’s own reserves.

In both the newest mitochondrial transfer methods and the cytoplasmic transfer experiments of over a decade ago, you have DNA from three individuals, but only two (from the maternal egg and sperm) contributed DNA that codes for traits and wresults in the inheritance of traits like eye color, hair color, skin color etc. The donor contributed mitochondrial DNA does not pass on donor traits but does give the resultant child a normal energy generating system. So, I suppose you can say that the child does have DNA from three individuals but it’s a bit of a stretch to say the baby has three parents.

The other interesting thing about mitochondria is the endosymbiotic hypothesis for the origin of mitochondria. This theory suggests that mitochondria originate from a specialized bacteria that was incorporated (via endocytosis) by another cell type, and became a permanent part of the other cell type’s cytoplasm. So hopping from one cellular organism  to another cellular organism is nothing new for mitochondria.

Next post: what are the safety and ethical implications of this brave new world?

References and more Info:

Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases.Paula Amato, M.D.,Masahito Tachibana, M.D., Ph.D.,Michelle Sparman, M.S.,and Shoukhrat Mitalipov, Ph.D.Fertility and Sterility
Volume 101, Issue 1 , Pages 31-35, January 2014

Epigenetic and experimental modifications in early mammalian development: Part II. Cytoplasmic transfer in assisted reproduction.Jason A.Barritt, Steen Willadsen, Carol Brenner and Jacques Cohen Human Reproduction Update, Vol.7, No.4 pp. 428±435, 2001

Genetics Home Reference: Mitochondria

All About Mitochondria

OvaScience

 

© 2014, Carole. All rights reserved.

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