With the rapid growth in science and technology, there has been a marked growth in emerging technologies. Various technologies have flooded the market in every field. Mitochondrial Replacement Therapy(MRT) is one such technology in the field of biotechnology that has the potential to change the very dynamics of newly emerging reproductive technology. One in 5,000 individuals has a genetic mitochondrial disease. The increasing prevalence of mitochondrial disorders resulting in significant morbidity and mortality combined with the higher potential of genetic transmission to the next generation are the factors that are expected to drive the market growth for such therapies. Many countries are in line to legalise such therapies. However, ethical concerns remain which need to be looked into to make this therapy legal.
What are mitochondria?
Mitochondria are small structures present in cells that produce much of the energy required by the cell. They contain a small amount of DNA that is inherited exclusively from the mother through the mitochondria present in her eggs. Mutations in this mitochondrial DNA (mtDNA) can cause a range of rare but serious diseases that can be fatal.
What are mitochondrial diseases?
Mitochondrial diseases are chronic (long-term), genetic, often inherited disorders that occur when mitochondria fail to produce enough energy for the body to function properly. (Inherited means the disorder was passed on from parents to children.) Mitochondrial diseases can be present at birth, but can also occur at any age. These diseases include severe disorders like Leigh syndrome, subacute sclerosing encephalopathy, neuropathy, ataxia, etc
What is Mitochondrial Replacement Therapy (MRT)?
It is a new form of reproductive in vitro fertilization that works on the principle of replacing a woman’s abnormal mitochondrial DNA (mt-DNA) with the donor’s healthy one.
Why is it done?
Women who carry a mitochondrial genetic defect risk passing on severe mitochondrial disease to their biological children. There are several diseases associated with defective mitochondria which are also the significant reason for the failure of metabolically active body organs like the heart, lungs, kidney, brain, and muscles etc. The development of a healthy baby free from genetic disorders and to terminate the lethal mitochondrial disorders are the chief motive of this technique. It aims to avoid the transmission of abnormal mitochondrial DNA from the mother to the child.
Techniques used in MRT
- Pronuclear Transfer(PNT) Technique – In PNT, two embryos are created, one with a mother’s egg which contains abnormal mitochondria, the other with a donor egg which contains normal mitochondria. The nuclear DNA is removed from each embryo. The nuclear DNA from the abnormal embryo is then transferred to the healthy embryo. The two original embryos are destroyed in the process of creating the third.
- Maternal Spindle Transfer (MST) Technique – In MST, the nuclear DNA is removed from the intending mother’s unfertilized egg and inserted in the donor’s egg which has had its nuclear DNA removed. The reconstructed egg is then fertilized to create an embryo free of abnormal mitochondria. This approach is preferable because the maternal spindle contains little cytoplasm which eventually reduces the chances of mt-DNA carryover and mutations.
- Polar Body Genome Transfer (PBT) technique – Polar body nuclear transfer has also been proposed as a potential MRT in mice. Polar bodies are formed during the process of egg maturation and fertilisation; they contain mostly DNA(genomic)in the form of chromosomes, with very little surrounding material (cytoplasm). Considering that a polar body contains few mitochondria and shares the same genomic material as an oocyte, polar body transfer is performed to prevent the transmission of mtDNA variants.
- Severe mitochondrial disease can have devastating effects which include the premature death of children, painful and debilitating and disabling conditions, and long-term ill-health and poor quality of life. It is hoped that mitochondrial replacement could prevent some children from suffering from a potentially very severe and sometimes life-threatening disease.
- Many couples tend to avoid pregnancy owing to the fear of passing dreadful diseases to their offspring. In this case, MRT can be helpful and couples can enjoy the right of being parents to a healthy child. It provides conceptive freedom to women.
- As other techniques such as surrogacy have limitations, MRT can prove to be helpful to couples affected by mitochondrial diseases.
- This may be beneficial to patients of advanced maternal age, who have a low oocyte yield or are poor responders, commonly observed in ART( Assisted Reproductive Technology) cycles.
- It can be also helpful to lesbian couples who wish to bestow their genetic portion to their child. This can be done by taking the nuclear genome of one partner and the mitochondrial genome of the other.
- The technique itself does not guarantee the complete removal of “Faulty Mitochondria” as the complete extraction of the nucleus without some mitochondria remaining attached to it is tricky even for experts.
- The extent of mutation and frequency of division of faulty mitochondria depends on the kind of disease. If these faulty mitochondria find their way into the embryo, it will tip off the balance between healthy and faulty mitochondria and the disease may continue in the subsequent generations.
- There may also be a risk of mismatch between the mtDNA haplotype of the surrogate and the donor mother.
- The technology can be misused for business purposes.
- Ethical issues are there which include changes to the subsequent generations if the child is female. The use of early embryos in PNT which involves the destruction of the extra embryo (that came from the fusion of sperm and ovum of the parents) which had the potential to develop into a healthy individual is another ethical issue.
- There are debates on the child formed as it has the DNA from three parents and religious opposition on the grounds of human’s meddling with the natural processes.
- Social issues include the belief that such technologies can only benefit the poor. Children born out of such techniques may be subject to social discrimination on the grounds of being three-parent babies.
- Many argue that it will not help those who are already born with mitochondrial diseases.
- As a genetic contributor at the biological level, the donor may claim to be a parent in the future, making it a risky procedure
- Another concern is that, by creating a new mix of genetic material, embryologists are creating lasting genetic changes that will be passed down through generations, before we have a chance to find out if they are dangerous.
- Some argue that this germline editing could eventually lead to “designer babies.”
- Egg donation requires powerful hormone therapy, stoppage of normal ovarian functions, superovulation for the woman to provide eggs, hormones to release matured eggs from the ovaries and minor surgery to remove them from the body. The process may even lead to death, which cannot be compensated for. Therefore, there is a high risk involved.
Scope in India
MRT as a technique has not been much explored in India to date but there are huge possibilities of its success in India. There is a lack of reliable data on the prevalence of mitochondrial diseases in India. Although there are possibilities of its success in India, there are numerous challenges as well given the Indian mindset and social setup. First is the general perception among people to have infant’s descent and genetic connection with parents and secondly, the desire and social pressure to conceive a genetic child. The very fact that assisted reproductive technologies(ARTs) have not gained much popularity in India, it will be a difficult task to break the orthodox beliefs for the success of this technology yet MRT comes as a hope to those women who aspire to be a mother to a healthy child.
Human mitochondrial disorders are among the most common genetic diseases, affecting around one in 6500 people. They are believed to be the reason behind 150 known conditions. MRT is a boon of hope for us as it is highly effective in the correction of mitochondrial defects leading to reproductive disorders and other diseases without losing our indigenous germplasm. Lack of curative treatments and prenatal diagnosis had led to an alarming situation that can be prevented through mitochondrial replacement therapy. However, more research needs to be carried out to ensure the safety and efficacy of the novel technology. The future holds a lot for this technology to grow.
- What do you know about Mitochondrial Replacement Therapy? What are the risks and benefits associated with it?