title: Attitudes toward prevention of mtDNA-related diseases through oocyte mitochondrial replacement therapy.
abstract: OBJECTIVE
  Among women who carry pathogenic mitochondrial DNA (mtDNA) point mutations and healthy oocyte donors, what are the levels of support for developing oocyte mitochondrial replacement therapy (OMRT) to prevent transmission of mtDNA mutations?
  
  
  CONCLUSIONS
  The majority of mtDNA carriers and oocyte donors support the development of OMRT techniques to prevent transmission of mtDNA diseases.
  
  
  BACKGROUND
  Point mutations of mtDNA cause a variety of maternally inherited human diseases that are frequently disabling and often fatal. Recent developments in (OMRT) as well as pronuclear transfer between embryos offer new potential options to prevent transmission of mtDNA disease. However, it is unclear whether the non-scientific community will approve of embryos that contain DNA from three people.
  
  
  METHODS
  Between 1 June 2012 through 12 February 2015, we administered surveys in cross-sectional studies of 92 female carriers of mtDNA point mutations and 112 healthy oocyte donors.
  
  
  METHODS
  The OMRT carrier survey was completed by 92 female carriers of an mtDNA point mutation. Carriers were recruited through the North American Mitochondrial Disease Consortium (NAMDC), the United Mitochondrial Disease Foundation (UMDF), patient support groups, research and private patients followed at the Columbia University Medical Center (CUMC) and patients' referrals of maternal relatives. The OMRT donor survey was completed by 112 women who had donated oocytes through a major ITALIC! in vitro fertilization clinic.
  
  
  RESULTS
  All carriers surveyed were aware that they could transmit the mutation to their offspring, with 78% (35/45) of women, who were of childbearing age, indicating that the risk was sufficient to consider not having children, and 95% (87/92) of all carriers designating that the development of this technique was important and worthwhile. Of the 21 surveyed female carriers considering childbearing, 20 (95%) considered having their own biological offspring somewhat or very important and 16 of the 21 respondents (76%) were willing to donate oocytes for research and development. Of 112 healthy oocyte donors who completed the OMRT donor survey, 97 (87%) indicated that they would donate oocytes for generating a viable embryo through OMRT.
  
  
  CONCLUSIONS
  Many of the participants were either patients or relatives of patients who were already enrolled in a research-oriented database, or who sought care in a tertiary research university setting, indicating a potential sampling bias. The survey was administered to a select group of individuals, who carry, or are at risk for carrying, mtDNA point mutations. These individuals are more likely to have been affected by the mutation or have witnessed first-hand the devastating effects of these mutations. It has not been established whether the general public would be supportive of this work. This survey did not explicitly address alternatives to OMRT.
  
  
  CONCLUSIONS
  This is the first study indicating a high level of interest in the development of these methods among women affected by the diseases or who are at risk of carrying mtDNA mutations as well as willingness of most donors to provide oocytes for the development of OMRT.
  
  
  BACKGROUND
  This work was conducted under the auspices of the NAMDC (Study Protocol 7404). NAMDC (U54NS078059) is part of the NCATS Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR) and NCATS. NAMDC is funded through a collaboration between NCATS, NINDS, NICHD and NIH Office of Dietary Supplements. The work was also supported by the Bernard and Anne Spitzer Fund and the New York Stem Cell Foundation (NYSCF). Dr Hirano has received research support from Santhera Pharmaceuticals and Edison Pharmaceuticals for studies unrelated to this work. None of the other authors have conflicts of interest.
  
  
  BACKGROUND
  Not applicable.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelstad
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Sklerov
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kriger
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sanford
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: Johnston
authors.initials: J
authors.lastname: Grier
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ash
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA The New York Stem Cell Foundation Research Institute, New York City, NY 10032, USA.
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: John L P
authors.initials: JL
authors.lastname: Thompson
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Sauer
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA mh29@columbia.edu.
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D000328:Adult; D001290:Attitude; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000737:chemistry; D005260:Female; D006579:Heterozygote; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics / Q000517:prevention & control* / Q000523:psychology; D000069321:Mitochondrial Replacement Therapy / Q000523:psychology*; D017354:Point Mutation
chemical_list: D004272:DNA, Mitochondrial
keywords: genetic disorders; in vitro fertilization; mitochondria; mitochondrial DNA; mitochondrial disease; mitochondrial replacement therapy; mtDNA; nuclear transfer; oocyte