Mitochondrial Replacement Therapy (MRT)

Mitochondrial Replacement Therapy (MRT)

Subject : Science and technology

Section: Biotechnology

Concept :

• Mitochondrial replacement therapy (MRT) is a new form of reproductive invitro fertilization (IVF) which works on the principle of replacing a women’s abnormal mitochondrial DNA (mt-DNA) with the donor’s healthy one.

What are Mitochondrial Disorders?

Just as our bodies have organs that perform particular functions, each cell within the body has small structures, aptly termed organelles, which have specific, life-sustaining jobs. For example, one of the primary organelles in each cell is the nucleus, which contains our DNA, or genetic information. Another type of organelle is mitochondria, which function to provide our cells, and thus our bodies, with energy. Interestingly, mitochondria also contain a very small amount of DNA, making them the only organelle other than the nucleus to house genetic information

Similar to nuclear DNA, mitochondrial DNA serves an important purpose, namely providing the genetic blueprint for molecular machines called proteins that carry out cellular functions. However, this capacity of mitochondria to carry DNA also makes them a genetic liability of sorts. Specifically, just like nuclear DNA, mitochondrial DNA is susceptible to mutations in the DNA code that can cause disease. If these DNA mutations lead to the production of damaged mitochondrial proteins, they can cause a class of diseases termed mitochondrial disorders.

Mitochondrial disorders are fairly common, affecting at least 1 in 5,000 births in the United States, and they exhibit a very unique inheritance pattern. Unlike nuclear DNA, which is passed in equal parts to a child from both parents, mitochondria are inherited solely from mothers. As such, if a mother has damaged mitochondrial DNA, she will pass this on to all of her children causing disease of a varied severity depending on the proportion of healthy and damaged mitochondria the child randomly inherits

To avoid this, scientists have developed techniques that allow them to use mtDNA from a donor, along with DNA from a mother and father. These are generally called mitochondrial replacement therapies, or MRT.

There are a few different ways of doing this, but most teams use one of two approaches. Some scoop out the nuclei of two eggs, one from a prospective parent and one from a donor. Then they put the would-be parent’s nucleus into the egg of the donor, which still contains the cytoplasm, the fluid outside the nucleus that holds the mitochondria. The resulting egg can then be fertilized with sperm, creating an embryo that technically has three genetic parents.

Step-by-Step Process –

• First, sperm from the father is used to fertilise eggs from the affected mother and a healthy female donor.
• The nuclear genetic material from the donor’s egg is then removed and replaced with that from the couple’s fertilised egg.
• The resulting egg has a full set of chromosomes from both parents, but carries the donor’s healthy mitochondria instead of the mother’s faulty ones.
• This is then implanted in the womb.
• The resulting baby has DNA from the mother and father as usual, plus a small amount of genetic material – about 37 genes – from the donor.
• The process has led to the phrase “three-parent babies”, though more than 99.8% of the DNA in the babies comes from the mother and father.
• The development of healthy baby free from genetic disorders and to terminate the lethal mitochondrial disorders is the chief motive of this technique.

Is MRT Procedure Risk-Free?

• The procedure is not without risks.
• Recent research has found that in some cases, the tiny number of abnormal mitochondria that are inevitably carried over from the mother’s egg to the donor egg can multiply when the baby is in the womb.
• So-called reversion or reversal could lead to a disease in the child.
• So far, the clinical experience with MRT has been encouraging, but the number of reported cases is far too small to draw any definitive conclusions about the safety or efficacy.
• Long-term follow-up of the children born through MRT is essential.

Legality of MRT:

• The United Kingdom, in 2016, became the first country in the world to legalise MRT.
• Last year, Australia became the second country to approve this therapy.
• In the United States, the therapy is illegal as it is considered as a form of genetic modification, and changes made to eggs, and sperm and embryos — known as germline modification — can be passed on to future generations.

Mitochondrial Diseases

• Certain defects might occur impacting on the way the mitochondria produces energy for the cells (Specially in the ‘energy-hungry’ tissues of the brain, nerves, muscles, kidneys, heart, liver), and thereby impacting cell function.
• The diseases that arise out of such mitochondrial mutations are called mitochondrial diseases.
• When the mitochondria are impaired and do not produce sufficient energy, that affects how the organs function, leading to a broad assortment of symptoms across the body, including brain damage, organ failure and muscle wastage.
• Mitochondria makes up less than 0.0005% of our entire DNA. But since the child receives it only from the mother, any aberrations in her mitochondrial DNA that may cause diseases is passed on completely to the child.
• According to the New York Stem Cell Foundation Research Institute, approximately 1 in 5,000-10,000 children are born each year with mitochondrial disease.