Mitochondrial Disease and Ivf

In vitro fertilization (IVF) is a technique that bypasses some forms of fertility by manually combining egg and sperm outside the womb, and then implanting the embryo in the uterus to be carried to term by the mother. Researchers have recently honed the technique in attempts to also use it to limit inherited diseases.

Some background information is necessary to understand the premise of the procedure.

The DNA carried within the cell nucleus is well known, and well studied in recent years since the human genome project, but humans also carry a second genome, mitochondrial DNA, which is passed down from mother to child in the cytoplasm of a woman’s eggs. Human mitochondrial DNA carries genes that encode proteins involved in mitochondrial function, roughly 37 of the estimated 3000 genes necessary for mitochondria to function. The mitochondria are the energy powerhouses of the cell, responsible for cellular respiration and ATP production, which is used in many other aspects of cell function. Damage to this system because of genetic defects is incurable.

Many of the genes responsible for mitochondrial function (estimated to be approximately 95% of all genes needed for mitochondrial function) are specific to certain cell types, making some inherited mitochondrial diseases tissue-specific (i.e. heart, muscle, or liver). Mitochondrial disease is more common in children as an inherited condition, but adult onset can sometimes occur depending on the specific disorder.

Because some mitochondrial diseases are inherited through the mother’s mitochondria in the egg, placing the fertilized nucleus from the biological mother into an anucleated egg with healthy mitochondria can eliminate some forms of inherited disease.

Three person IVF consists of two eggs from two women and sperm from one man. The mother’s egg is fertilized with the sperm, which causes chromosome combination in the nucleus. The other egg from a donor has the nucleus removed. The nucleus from the fertilized egg is then placed in the donor egg within a day to allow it to develop normally, passing on healthy mitochondria from the donor rather than the aberrant mitochondria of the mother.

There are some problems with this procedure. 1) The child will get genetic information from the donor via the mitochondria. This is an ethical issue for many people. 2) Not all mitochondrial diseases are only caused by mitochondrial DNA, and they are still poorly understood to some extent, 3) and determining which children may have disease from which mothers is still uncertain. All in all, this procedure may, at some point in the future, prevent some inherited diseases that can be determined prior to fertilization. But it is extremely limited at the present time.

The British researchers view their success as a proof of concept to one day challenge mitochondrial disease.

For more information on mitochondrial diseases and treatments, see the United Mitochondrial Disease Foundation.