Mitochondrial Donation

Conventional babies are concoctions born of the blending of genetic material from two people. This is not the case for a unique baby boy, who was born in April 2016 to Jordanian parents, conceived in Mexico, with the help of American doctors. What made this cross-continental effort revolutionary was that the baby had 99.9% of the genetic material of his parents, and 0.1% of the genetic material of a donor. But this small percentage is what made him healthy.

The couple’s previous attempts at having children were cruelly truncated while still in the womb, or, lost at a very young age. This was because the woman carried certain deleterious genes (mutations) in her mitochondrial DNA (mtDNA). This caused her children to develop Leigh’s disease, which is a debilitating and destructive disease that destroys the central nervous system, killing the sufferer. Given that mtDNA codes for 37 distinct genes, Leigh’s disease is just one of the possible manifestations of mutations that can occur in these genes.

Mitochondria are known as the energy generators of cells. Every cell in the human body has an abundance of these specialised cell components, which reside in the gel-like liquid found inside cells called the cytosol. They are essential to the survival of cells, because, without the energy generated by these powerhouses, a cell cannot function appropriately and or at all, and may die. This is what occurs if a person has a mitochondrial disease.

Unfortunately, this suite of diseases that fall under this categorisation is so myriad, that, at a time, one or multiple organs can be affected. Thus far, only 100 diseases have been identified. These include diseases that incapacitate the nerves of the eyes resulting in vision loss, cause heart failure or stroke-like episodes. There will undoubtedly be more to be uncovered. However, even the existing diseases have not been researched extensively enough which means that there are no current well-defined cures or treatments.

However, medical science has devised a way to prevent the inheritance of mitochondrial diseases through assisted reproductive techniques (ARTs) known as mitochondrial replacement techniques (MRTs). There are two separate procedures that come under the umbrella term of MRT. The first is termed pronuclear transfer (PNT) and the second is called maternal spindle transfer (MST).

PNT involves the manipulation of zygotes or fertilised cells, formed when a sperm fertilises an egg. In PNT, two separate ‘types’ of zygotes are manipulated. Type one is produced by fertilising the egg of the intended mother with sperm from the intended farther. The second type is
produced using an egg from a donor, who does not carry any mutations for mitochondrial disease in her egg cells, and fertilising this with the intended farther’s sperm.

Before any of these fertilised eggs can develop into embryos, the genetic material of the egg donor is discarded from within the fertilised cell. Then, using the genetic material of the intended parents, and the fertilised cell produced from the donor as a casing, (which only contains her healthy mitochondria), a zygote is produced and implanted into the intended mother.

On the other hand, MST involves tinkering with oocytes or immature egg cells obtained from the intended mother and healthy donor. The chromosomes contained within the oocytes, which carry all the maternal genetic information are found congregated to one side of the oocyte during a particular phase of cell division which makes them ripe for the plucking. The genetic material of the to-be-mother is inserted into the genetic material-free oocyte of the donor. This newly created healthy oocyte is then fertilised using the sperm from the to-be-father, to give a zygote, which is implanted into mother.

There are two lesser known methods called polar body transfer and germinal vesicle transfer, both of which are types of maternal spindle transfer, and involve manipulating the immature egg cells at various stages of its development. These techniques are still being
researched more thoroughly before they can be approved for use.

All this may sound terribly futuristic, and even scary, given the levels of genetic manipulation involved. But PNT and MST are already happening in the UK. These types of MRT were legalised via a parliamentary vote as recently as 2015. Two women, who carry mutations which could cause their babies to develop MERRF syndrome, which affects multiple organs, causing seizures, loss of muscle control and dementia, were selected to undergo MRT in Newcastle Fertility Centre early this year.

Progress like this might provide the impetus for other countries like Australia to consider legalising MRT. In fact, it is known that approximately 60 people in any given year will develop severe cases of a mitochondrial disease, and many more will have to live with milder forms. This makes it an important health issue to consider.

Hearteningly, on the 27th of June, the Senate Community Affairs References Committee made an independent recommendation that mitochondrial donation is allowed by law, taking the first important step to make Australia the second country in the world to allow this procedure. The experts who made up the committee concluded that the legalities could be eased by tasking the National Health and Medical Research Council—the Australian body responsible for providing advice on the ethics of all health and medical research— with investigating the safety of MRT in an Australian context. They also acknowledged the reproductive specialists in this country are more than capable of handling the intricacies of MRT.

There are also independent organisations such as the Australian Mitochondrial Disease Foundation (AMDF), which do a lot to increase awareness of mitochondrial diseases and raise much-needed funds for research. The AMDF estimates that the healthcare costs for a child with mitochondrial disease can cost the National Disability Insurance Scheme (NDIS) and hence the taxpayer, around 120 000 AUD per month. Similarly, the costs of medical tests, healthcare and disability services for adults too can be exponential.

So, it would seem that it is now in the hands of the government as to whether and if so, how fast, they will act on this recommendation of the Senate Community Affairs References Committee in order to take ART in Australia into the future.

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