Development of mitochondrial replacement therapy

Development of mitochondrial replacement therapy

News Analysis   /   Development of mitochondrial replacement therapy

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Published on: May 15, 2023

Source: NIH

Context:

The Human Fertilisation and Embryology Authority (HFEA), the U.K. fertility regulator, recently confirmed that less than five children have been born using mitochondrial replacement therapy (MRT) as of April 2023.

About Mitochondria

Mitochondria are organelles found in eukaryotic cells.

They are often referred to as the “powerhouses” of the cell because they generate most of the cell’s energy.

Structure

Mitochondria have a double membrane: an outer membrane and an inner membrane

The inner membrane is highly folded to form cristae, which increase the surface area available for energy production

The space between the two membranes is called the intermembrane space

The interior of the mitochondrion is called the matrix, which contains enzymes involved in energy production

Function

The primary function of mitochondria is to produce ATP (adenosine triphosphate), the molecule that cells use for energy.

Mitochondria do this through a process called cellular respiration, which involves the breakdown of glucose and other molecules to generate energy.

Mitochondria also play a role in other cellular processes, such as calcium signaling and apoptosis (programmed cell death)

Mitochondrial dysfunction has been linked to a variety of diseases, including cancer, diabetes, and neurodegenerative disorders.

Replication

  • Mitochondria replicate through a process called fission, in which the organelle divides into two.
  • Mitochondria also have their own DNA (mitochondrial DNA or mtDNA) and can replicate independently of the cell’s nucleus.
  • Mutations in mtDNA can lead to mitochondrial diseases, which can affect energy production and other cellular processes.

About Mitochondrial Replacement Therapy

Mitochondrial Replacement Therapy (MRT) is a new form of reproductive in-vitro fertilization (IVF) that involves replacing a woman’s abnormal mitochondrial DNA (mt-DNA) with a donor’s healthy mt-DNA.

Purpose: MRT is primarily performed to prevent women who are carriers of mitochondrial diseases from passing on these heritable genetic diseases to their children.

DNA Types: Humans have two types of DNA in their cells: nuclear DNA, inherited from both parents, and mitochondrial DNA (mtDNA), inherited only from the mother.

In 2015, the United Kingdom became the first country to regulate MRT, establishing legal and ethical guidelines for its use.

Procedure:

The process of MRT involves the following steps:

  1. An egg donor without mitochondrial DNA mutations is selected.
  2. The nucleus of the egg from the woman with mitochondrial DNA mutations is removed.
  3. The nucleus of the donor egg is transferred into the egg of the woman with mitochondrial DNA mutations, replacing the nucleus with abnormal mtDNA.
  4. The resulting egg, containing the nuclear DNA of the woman and the healthy mtDNA of the donor, is fertilized with the father’s sperm in the embryology lab.
  5. If the fertilized egg develops into a viable embryo, it can be transferred during IVF treatment, ensuring that the embryo is free from mitochondrial disease.
  6. It is important to note that MRT is a complex and controversial procedure with ethical and scientific considerations. Its use is typically limited to cases where the risk of transmitting severe mitochondrial diseases is high. The long-term effects and outcomes of MRT are still being studied, and its availability may vary by country due to different regulations and guidelines.

What is in-vitro fertilization (IVF)?

  • In-vitro fertilization (IVF) is an assisted reproductive technology (ART) in which fertilization of an egg and sperm takes place outside the human body.
  • This complex procedure involves the retrieval of eggs from the ovaries and their manual combination with sperm in a laboratory to achieve fertilization.
  • Following fertilization, the resulting embryo is then transferred to the uterus, where implantation into the uterine wall can lead to pregnancy.
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