Medical science continues to advance, offering new possibilities for families to address inherited genetic conditions. Prospective parents often prioritize the health and well-being of their future children. This drives ongoing research into methods that can prevent the transmission of certain genetic disorders, providing hope and expanded reproductive choices. Modern technologies enable interventions at very early stages of development to achieve this aim.
Understanding Leber’s Hereditary Optic Neuropathy (LHON)
Leber’s Hereditary Optic Neuropathy (LHON) is a rare genetic disorder causing vision loss, often beginning in young adulthood (ages 12-30). The condition causes a painless, subacute loss of central vision, usually affecting one eye first, followed by the other within weeks or months. This progressive vision impairment results from the degeneration of retinal ganglion cells and their axons, which form the optic nerve responsible for transmitting visual information to the brain.
LHON is caused by specific mutations in mitochondrial DNA (mtDNA). Mitochondria are structures within cells that produce energy and carry their own distinct genetic material. Unlike nuclear DNA, which is inherited from both parents, mitochondrial DNA is inherited exclusively from the mother. Therefore, all children of a mother carrying an mtDNA mutation will inherit it, though not all carriers develop symptoms. Males are affected by vision loss more frequently than females, with an approximate male-to-female ratio of 4:1.
In Vitro Fertilization and Genetic Screening
In Vitro Fertilization (IVF) is a medical procedure where eggs are fertilized by sperm in a laboratory. This process involves retrieving multiple eggs from the woman, fertilizing them, and allowing the resulting embryos to develop for several days in culture. This step creates an opportunity for early genetic assessment before any embryo is transferred to the uterus.
During IVF, embryos can undergo Preimplantation Genetic Testing (PGT), previously known as Preimplantation Genetic Diagnosis (PGD). PGT screens embryos for specific genetic abnormalities or chromosomal disorders prior to implantation. Fertility specialists use PGT to identify embryos free from these defects, aiming to reduce the risk of failed implantation, miscarriage, or the birth of a child with a severe genetic condition. This diagnostic step allows for the selective transfer of unaffected embryos into the woman’s uterus.
Specific Methods for Preventing LHON Transmission
Preventing LHON transmission presents a unique challenge because the condition stems from mitochondrial DNA mutations, not nuclear DNA typically screened by standard Preimplantation Genetic Testing (PGT). Since mitochondria are inherited solely from the mother, traditional PGT methods are not effective for selecting embryos free of mitochondrial disease, as all embryos from an affected mother will carry the mutated mitochondrial DNA. To address this, Mitochondrial Replacement Therapy (MRT) is employed with IVF.
MRT involves replacing the mother’s mutated mitochondria with healthy mitochondria from a donor egg. Two primary techniques for MRT are Maternal Spindle Transfer (MST) and Pronuclear Transfer (PNT). In Maternal Spindle Transfer, the nuclear DNA is removed from the mother’s unfertilized egg. This spindle is then transferred into a donor egg that has had its own nucleus removed but contains healthy mitochondria. The reconstituted egg is then fertilized with the father’s sperm in vitro.
Alternatively, Pronuclear Transfer occurs after fertilization. Both the mother’s egg and a donor egg are fertilized with sperm. Before the paternal and maternal genetic material fuse within the fertilized egg, the pronuclei are removed from the mother’s fertilized egg. These pronuclei are then transferred into the donor’s fertilized egg, from which its own pronuclei have already been extracted. In both MST and PNT, the goal is to create an embryo with the nuclear DNA of the intended parents but with healthy mitochondria from a donor, thereby circumventing the transmission of LHON.
Implications and Ethical Considerations
The application of Mitochondrial Replacement Therapy (MRT) to prevent conditions like LHON raises societal and ethical discussions. These procedures involve genetic material from three individuals—the nuclear DNA from both parents and the mitochondrial DNA from a donor—leading to the term “three-parent babies”. An ethical concern revolves around germline modification, as changes to mitochondrial DNA would be passed down to future generations. This raises questions about the long-term health, identity, and potential unforeseen effects on children born through these methods.
The legal and regulatory landscape for MRT varies across different countries. The United Kingdom became the first country to legally approve MRT in 2015, allowing its use under strict regulations. As of July 2025, eight babies have been been born using MRT in the UK. In contrast, the United States faces a different situation; clinical trials for MRT are unlikely to begin until the Food and Drug Administration (FDA) addresses safety concerns and a congressional ban on research involving heritable genetic modification of embryos is lifted.
Success rates for MRT are still being evaluated, and potential risks include the possibility of some faulty mitochondria from the mother being carried over into the new embryo, or adverse interactions between the donor mitochondrial DNA and the parents’ nuclear DNA. Families considering MRT also face emotional and financial considerations, given the complexity and cost of the IVF and MRT procedures. Despite these challenges and ongoing debates, these advanced reproductive technologies offer hope to families at high risk of transmitting severe mitochondrial diseases like LHON, offering a pathway to a genetically related child free from the condition.