MITOCHONDRIAL REPLACEMENT THERAPY (MRT)

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Context

• Eight years before U.K. became the first country in the world to approve a reproductive technique known as mitochondrial replacement therapy (MRT). But “less than five” children have been born using the procedure, as of April 2023.

All you need to know about Mitochondria

• A mitochondrion is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi.
• Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy. They were discovered by Albert von Kölliker in 1857.
• The term mitochondrion was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase coined by Philip Siekevitz in a 1957.
• Some cells in some multicellular organisms lack mitochondria (for example, mature mammalian red blood cells).
• A large number of unicellular organisms, such as microsporidia, parabasalids and diplomonads, have reduced or transformed their mitochondria into other structures.
• One eukaryote, Monocercomonoides, is known to have completely lost its mitochondria and one multicellular organism, Henneguya salminicola, is known to have retained mitochondrion-related organelles in association with a complete loss of their mitochondrial genome.
• Although most of a eukaryotic cell's DNA is contained in the cell nucleus, the mitochondrion has its own genome ("mitogenome") that is substantially similar to bacterial genomes.
• A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins.
• The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to a mitochondrion:
  • The outer mitochondrial membrane,
  • The intermembrane space (the space between the outer and inner membranes),
  • The inner mitochondrial membrane,
  • The cristae space (formed by infoldings of the inner membrane), and
  • The matrix (space within the inner membrane), which is a fluid.
  • Mitochondria have folding to increase surface area, which in turn increases ATP (adenosine triphosphate) production. Mitochondria stripped of their outer membrane are called mitoplasts.

About Mitochondrial replacement therapy (MRT)

• Mitochondrial replacement therapy (MRT), sometimes called mitochondrial donation, is the replacement of defective mitochondria in one or more cells to prevent or ameliorate disease.
• MRT originated as a special form of in vitro fertilization in which some or all of the future baby's mitochondrial DNA (mtDNA) comes from a third party.
• This technique is used in cases when mothers carry genes for mitochondrial diseases.
• The therapy is approved for use in the United Kingdom.

• In short, 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.
• Such diseases are rare, yet can be severely debilitating, progressive, and often fatal in infancy or childhood.

Mitochondrial Replacement Therapy: How it is done

The procedure involves several steps including:

1. Egg retrieval: The donor and recipient egg cells are obtained from two different women. The donor egg is typically from a young and healthy woman with no history of mitochondrial disease, while the recipient egg cell is from a woman with mitochondrial disease.
2. Nuclear transfer: The nucleus of the donor egg cell, which contains all of the genetic material except the mitochondrial DNA, is removed and transferred to the cytoplasm of the recipient egg cell, which contains healthy mitochondria.
3. Fertilisation: The reconstructed egg cell is then fertilised with sperm either through in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).
4. Embryo transfer: The resulting embryo is then transferred to the uterus of the recipient mother, where it will develop into a foetus.

Benefits of MRT

• MRT offers new possibilities for overcoming fertility challenges due to mitochondrial disease and could have a significant impact on the lives of couples struggling with infertility.
• MRT provides a way to prevent the transmission of these diseases without resorting to alternative options such as egg or embryo donation.
• It allows parents to maintain a biological relationship with their child, which can be an essential factor for many couples.

Ethical Controversy

• Many experts have expressed concerns about safety of the technique as well.
• There has been very little animal testing, much less human tests, and only 5 babies have been born from MRT.
• Most scientists don’t want unregulated MRT, and view the regulatory approach in the U.K. to be a model for safely exploring the treatment. Last year, Australia became the second country to approve this therapy.

PRACTICE QUESTION Q. Consider the following statements 1. One eukaryote, Monocercomonoides, is known to have completely lost its mitochondria. 2. The mitochondrion has its own genome ("mitogenome") that is substantially similar to bacterial genomes. Which of the above statements is/are incorrect? (a) Only 1 (b) Only 2 (c) Both 1 and 2 (d) Neither 1 nor 2 Correct Answer: (d) Neither 1 nor 2

https://www.thehindu.com/sci-tech/uk-sees-success-in-mitochondrial-replacement-therapy/article66845829.ece