Prevention of Mitochondrial Disease Caused by mtDNA Mutation through Mitochondrial Replacement Therapy (MRT)

Objective: We investigated the role of MRT in preventing mitochondrial diseases caused by mtDNA mutation. Method: MRT was conducted by spindle nuclear transfer (SNT) between human oocytes. Mutant mtDNA load was analyzed. Results: of 18 oocytes collected from a female carrier (24.5% mtDNA 8993T>G) of Leigh Syndrome, 7 oocytes (haplogroup I) were attempted for MRT to enucleated donor oocytes (haplogroup L2c). Of the 4 blastocysts created from the 5 reconstituted oocytes, 1 euploid embryo was achieved, carrying 5.73% mtDNA 8993T>G mutation load comparing to 3.66% in an aneuploid embryo. The calculated mtDNA 8993T>G load was about 100% in both carrier’s oocytes, from which the above two embryos were created.  A boy was delivered after euploid embryo transfer to the carrier. The mutant mtDNA load was differentiated expressed among the fetal and fetal appendage tissues, ranging from 0% to 9.23%. The child is still asymptomatic of Leigh Syndrome or other diseases at 5-month old now. Conclusions: Mitochondrial disease caused by mtDNA mutation may be prevented by MTR through SNT among different haplogroups. More cases and a long term follow-up are warranted to evaluate the safety of this technique.