Avoiding mixtures of different mitochondria leads to effective mitochondrial replacement May 25, 2016, 14:53

Now, scientists at the NYSCF Research Institute and Columbia University are working to hone this technique and understand the biological processes that would impact patients as this process is brought into clinical trials. Mitochondria function as cellular batteries. People born with malfunctioning mitochondria experience a spectrum of symptoms potentially resulting in childhood death, including stunted development, neurological disorders, heart disorders, and stomach and digestive problems. Published in Cell Stem Cell, Dr. Dieter Egli, Senior Research Fellow at the NYSCF Research Institute and an assistant professor at Columbia University College of Physicians and Surgeons, and his colleagues transferred nuclear DNA into cells from different donors to understand more about MRT and its clinical applications. Dr. Egli explained, «This is one more step towards the therapeutic application of mitochondrial replacement and informs us how MRT is best conducted clinically.» 

Working in close collaboration with Drs. Michio Hirano and Mark Sauer and their teams at Columbia University Medical Center, this research continues to lay the groundwork for future clinical trials by showing that mitochondria from an individual can successfully be replaced with mitochondria from any unrelated donor. They found that nuclear DNA and mitochondrial DNA from different individuals are compatible. This alleviates a common concern regarding MRT- that replacing diseased mitochondria with healthy mitochondria from a different individual may prove incompatible-and brings a critical piece of information requisite to translating this innovative preventive treatment to patients waiting to build families. 

«For women who are affected with these diseases, this work brings hope that they will have access
to therapies that will allow them to have healthy children. Since our initial work with MRT, we have
advocated for the FDA to permit clinical trials that enable women to prevent their children from
inheriting mitochondrial diseases. I hope this research provides further evidence to the FDA to
approve this work for clinical application," explained Susan L. Solomon, Co-Founder and CEO of
The New York Stem Cell Foundation. 

The researchers made an important discovery, finding that during the transfer of nuclear DNA into
donor cells with healthy mitochondria there may be some carry-over of mitochondria from the
donor individual’s cells. The resulting cells may contain two different types of mitochondria.
Sometimes the carried-over mitochondria decrease in quantity and becomes barely detectable or are
eliminated altogether as the cells grow and divide. However, in rare circumstances, these transferred
mitochondria increase in quantity as cells divide, negating the replacement of the affected
mitochondria. 

To combat the potential adverse outcome Dr. Egli, a NYSCF — Robertson Stem Cell Investigator
suggests, «In order to prevent the transmission of mitochondrial diseases, we need to avoid
competitive situations between mitochondrial genotypes of the parent and of the mitochondrial
donor. The co-existence of the two-mitochondrial types within one cell must be avoided through
minimizing or even eliminating carry-over during transfer.» 

Another important discovery from this work revealed that scientists can freeze the eggs that contain
the nuclear DNA for mitochondrial replacement. A key insight allowing doctors to avoiding having
to sync ovulation between the patient and donor for effective treatment when MRT is brought to
clinical trials. 

Dr. Mitsutoshi Yamada, formerly a Postdoctoral Fellow at the New York Stem Cell Foundation
Research Institute, was the first author on the study and is now at Keio University School of
Medicine in Japan.

Source: http://nyscf.org/pdfs2/NYSCF_PR_2016_05_19_Cell_Stem_Cell_Mitochondrial_Drift.pdf