No treatments exist for children born with mitochondrial diseases, but a series of discoveries in the OHSU Center for Embryonic Cell and Gene Therapy is making progress on a technique that prevents transmission of these often-fatal genetic diseases, which are passed on from mothers to their children. The latest findings were published on Nov. 30 in the journal Nature.
OHSU scientist Shoukhrat Mitalipov, Ph.D., led a team that successfully prevented transmission of genetic defects in mitochondrial DNA in the cells of monkeys in 2009 and in human cells in 2012.
In the procedure, mitochondrial replacement therapy, the mother’s nucleus is transferred into a donor’s egg that has had its nucleus removed. The resulting egg includes the donor’s healthy mitochondria and the mother’s nucleus. This nuclear DNA determines functions ranging from organ structure and appearance to personality and intellectual characteristics.
A persistent risk with the procedure is transferring small amounts of defective mitochondria from the mother’s DNA to the donor cell, which can result in a gradual return to the mutated mitochondria and mitochondrial disease.
The findings published today suggest a way to reduce this risk — selecting egg donors whose mitochondrial DNA is compatible with the mother’s ancestral mitochondria. Similar groups of mitochondrial DNA are known as haplotypes, each of which represents major branching points on the human genetic family tree. The team proposes setting donor mitochondrial DNA matching criteria to avoid a return of mutant mitochondria.
Mitochondrial mutations cause a range of diseases, many of which affect organs with high-energy demands such as the heart, muscle and brain. Currently, the U.S. government forbids clinical trials of mitochondrial replacement therapy. Britain has authorized such studies. The first baby treated with mitochondrial replacement therapy was born in Mexico earlier this year.
OHSU researchers who contributed to the study also include Eunju Kang, Nuria Marti Gutierrez, and Amy Koski, members of the Center for Embryonic Cell and Gene Therapy. See the complete list of authors.
Funders of the studies include the Leducq Foundation, OHSU institutional funds and Cincinnati Children’s Hospital Research Foundation.
Read the full OHSU news release.