Are We Finally Saying Goodbye to Inherited Mitochondrial Diseases? (Part 2)

Welcome back to this two-part series on mitochondrial diseases and types of Mitochondrial Replacement Therapy (MRT). In Part 1 (which you should read if you haven’t yet), we examined mitochondrial diseases and one type of MRT, cytoplasmic transfer (CT). But cytoplasmic transfer had a major flaw: the mitochondria couldn’t be fully replaced.

Today, we’re looking at how the other 3 types of treatment sought out to solve this problem, as well as the ethical and regulatory side of MRT and genetic modification as a whole.

Types of MRT (Continued)

In the 2000s, pronuclear transfer (PNT) would be developed by UK researchers (the same procedure mentioned in Part 1). Although sometimes referred by the media as ‘three-way IVF (three-way in-vitro fertilization)’, that’s not the most scientifically accurate term for this procedure, as it is a vague umbrella term that can also be applied to other types of MRT. This process involved fertilizing both the mother’s and donor’s egg, then transferring the pro-nuclei of the mother’s egg to the donor’s egg (with the pro-nuclei already removed). But the disadvantage of this procedure is that when the pro-nuclei is removed from the mother’s egg and transferred, some mitochondria still may be carried over as well. Despite this, the procedure is still being used and developed (unlike cytoplasmic transfer), is quite successful in replacing almost all of the mitochondria, and holds much potential for becoming the mainstream treatment for inherited mitochondrial diseases.

In the mid to late 2000s, yet another MRT procedure was introduced, called maternal spindle transfer (ST). In this procedure, an oocyte (an immature egg cell) is removed from the mother, and in metaphase II stage of cell division, the spindle-chromosome complex (which includes the genetic information of the mother) is removed and inserted into a donor oocyte with its spindle-chromosome complex already removed. This egg is then fertilized and allowed to form a blastocyst, and after an inspection of mitochondria, it can be placed inside the mother’s uterus. Maternal spindle transfer is quite similar to PNT in many ways, with both involving the removing and transfer of the genetic information of the mother. But this is much harder to pull of than PNT.

The newest addition to the family of MRT treatments was the Polar Body Transfer (PBT), a procedure that started research in the 2010s. Utilizing polar bodies (byproducts of meiosis) from the mother to further reduce the chances of mtDNA carryover, this treatment is still largely in the experimental stage than practical usage.

Ethics & Regulations Regarding MRT

Despite the life-saving potential for Mitochondrial Replacement Therapy, this type of procedure (and other types of genetic modification) have been under constant scrutiny ever since research started.

Many critics have long held the belief that any form of genetic modification (including MRT, which doesn’t alter physical appearance) is unethical, as researchers are messing with the fundamental building blocks of life and changing the genetic blueprint. Additionally, some critics fear that genetic modification could lead to genetic enhancement, not just preventing diseases - a reality where so-called ‘designer babies’ are prevalent, and traits such as intelligence, physical appearance and height can be altered and ‘customized’.

Regarding the specific case of PNT, it has raised concerns over the moral implications of changing the genetic inheritance of future generations and by creating ‘three-parent babies’. Furthermore, the still immature technology may have unintended consequences, such as interfering with mitochondrial inheritance patterns, causing mitochondrial mismatch (the effects of which we still can’t grasp clearly), etc.

Due to these concerns, governments around the world have taken significant action to regulate the industry of genetic modification as well as specific examples such as MRT. For example, the UK’s Human Fertilisation and Embryology Authority (HFEA) oversees MRT to prevent mitochondrial disease, after legislation passed in 2015 legally approved of the practice.

Conclusion

Despite mixed opinions about MRT and genetic modification in general, these technologies will undeniably change the lives of countless individuals for the better. However, the mainstream deployment of procedures such as MRT is still in its infancy, and one that needs persistent research and proper regulation in order to be achieved.

And that concludes this article. If you learned something new in this two-part series, please support my work by liking, subscribing, and sharing. Thank you for reading, and come back next week for more in-depth news analysis.