Preventing the Transmission of Mitochondrial Diseases Through Heteroplasmic Shift
Abstract
Topic Area: The proposed project relates to the Fiscal Year 2016 Peer Reviewed Medical Research Program Topic Area of “Mitochondrial Disease.” Mitochondrial myopathies are a group of devastating diseases caused by mutations in mitochondrial DNA (mtDNA). Mitochondrial diseases affect 1 in 5,000 children, and it is estimated that 1 in 200 women could be potential carriers of a mitochondrial disease. Mitochondrial diseases are characterized by the degeneration of tissues and organs with high energetic demands, including muscle and nerves. Currently, genetic counseling and preimplantation genetic diagnosis (PGD) are the best options for preventing the transmission of mitochondrial diseases. In this project, we aim to prevent the transmission of mitochondrial myopathies by the selective elimination of mutated mtDNA from oocytes. The technique is based on the introduction of nucleases (molecular scissors) into the oocyte. These nucleases then enter the mitochondria and specifically identify and eliminate the mutated mtDNA. Feasibility of this approach was recently demonstrated in mouse embryos, where the transmission of targeted mtDNA to the next generation was successfully prevented. Here we will use a similar strategy to selectively target and eliminate mutated mtDNA from human oocytes obtained from patients with a mitochondrial disease. Assessing the safety and efficacy of this approach is essential for moving this technology into the clinic in the near future. Moreover, results from this project will also further our understanding of the basic biology of mitochondrial diseases. In conclusion, results emerging from this project will potentially lead to the eradication of mitochondrial myopathies that affect thousands of families.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710552
Entities
People
- Juan Carlos Izpisúa Belmonte
Organizations
- Salk Institute for Biological Studies
- United States Army