~ Written By Surabhi Iyer
Mitochondrial replacement therapy (MRT, sometimes called mitochondrial donation)
is the replacement of mitochondria in one or more cells to prevent or ameliorate disease. It was first used in 1996 by the embryologist Jacques Cohen and others at the Institute for Reproductive Medicine and Science for a cytoplasmic transfer in a human assisted reproduction procedure. In 1997, the first baby was born using this procedure. However, due to ethical objections it has still not very widely come into practice.
It is a well-known fact, that mitochondria is the ‘power house of the cell’ and provides
energy for several of the complex metabolic reactions happening in our bodies on a daily
basis. The primary role of mitochondria is aerobic respiration, that is, oxidative
phosphorylation (OXPHOS) and the production of cellular energy in the form of
adenosine triphosphate (ATP). But, the same mitochondria if damaged due to any
external factor can pose a danger to humans and unfortunately many are unknown of
the dangers possessed by a fault in the mitochondria.
Our bodies are complex mechanisms and external factors can often affect our
mechanisms in dangerous ways. Mutation, one amongst the many examples, can be
extremely lethal to a person exposed to it. The patient who harbours pathogenic
mutations that can cause progressive and lethal diseases with no available cure is often
required to make difficult reproductive choices. The parents then have to switch to
other alternatives such as gamete/embryo donation, selecting normal embryos or
conceptus by genetic testing, or adoption. Although, it’s often observed parents prefer
to have their child with their own genetics and as a result their choices become
narrower and restricted to methods involving correcting the “faulty gene” in early
embryos called germ line germ therapy. However, the consequences of these are passed
on to future offspring irrespective of the modifications being positive or negative
rendering this to be a risky procedure.
The speciality of mitochondria is that they have their own DNA, known as the
Mitochondrial DNA (mtDNA). While we all inherit one set of chromosomes from both
our parents, it is not the same case with mtDNA. The offspring always inherit the mtDNA
only from the mother hence if the mother has mitochondrial diseases it is likely to be
passed on to the offspring too. Some nuclear transfer techniques, also referred to as
mitochondrial replacement therapy (MRT), are considered to be a potential germ line
gene therapy for inherited mitochondrial diseases. This therapy is primarily used for two
purposes the first one being, another form of in-vitro fertilisation wherein some, or in
some cases all, of the future baby’s mitochondrial DNA comes from a third party as the
mother may be a carrier of genes causing mitochondrial diseases. This technique is also
used when autologous mitochondria is used to replace mitochondria in damaged tissue
to restore the tissue to a functional state.
Muscle and nerve cells have especially high energy needs and as a result require a large
amount of mitochondria, hence muscular and neurological problems are common
features of mitochondrial diseases. Other frequent complications also involve impaired
vision, cardiac arrhythmia(abnormal heartbeat), diabetes, stunted growth etc. A fatal
syndrome that can also be passed on to offspring from parents having mitochondrial
diseases is Leigh syndrome. Leigh syndrome is a severe neurological disorder that
usually begins to shows its effects and becomes apparent within the first year of life. A
child suffering from this syndrome has progressive loss of mental and movement
abilities (psychomotor regression) and typically results in death within two to three
years, usually due to respiratory failure or in worse cases, even seizures.
The severity of mitochondrial diseases and its ability to be passed on to offspring makes
it integral to be able to find a possible cure to prevent such diseases. Although, the
parents may not evidently suffer from the disease themselves, being a carrier puts their
offspring at risk as the diseases are often untreatable and the symptoms can only be
alleviated however will continue to persist and eventually may lead to death.
Considering this, the MRT was developed to try and ensure that mitochondrial diseases
do not pass to offspring. MRT uses healthy mitochondria coming from a donor’s egg
whose nucleus has been removed and into which the mother’s nucleus is transferred. In
vitro fertilization (either before or after MRT) produces an embryo that contains nuclear
DNA from the father and the mother with healthy mtDNA from the donor.
However, despite the benefits of this procedure, there have been said to be
disadvantages too associated with this technique. For example, using a foreign donor
DNA in the mitochondria of the child could result in changes in personal traits as well as
metabolism in unforeseen ways. In addition to this, epigenetic effects can also prove to
be a hazard as these environmental influences can alter the way genes work, either
switching them on or off, to produce permanent changes. More so, it is argued that the
child may continue to have unidentified health risks as a side effect of the procedure
that may only be identified at later stages of his/her life and the concept of artificially
using donor mtDNA in the child proves to be a form of a ‘designer baby’ for some,
resulting in ethical objections.
Weighing all the pros and cons, it is although noteworthy that this process can indeed
give a new life to an unborn whose mother has a mitochondrial disease as otherwise it
wouldn’t be wrong to say that the unborn would have a very short life ahead. This
method is still in the process of being legalized in some countries while it has already
been legalized in some and as more tests are done and once the ethical issues and
disadvantages of this process are minimized, this technique is likely to be used by many
couples to secure healthy future for their unborn child.
Mitochondrial Replacement Therapy Process
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