Spindle Replacement Therapy Prevents Transmission of Inherited Mitochondrial Diseases

In the future, inherited diseases caused by mutations in mitochondrial DNA (mtDNA) may be avoided by the use of a novel gene therapy technique that transfers a defective egg's genome into an enucleated egg with healthy mtDNA.

Approximately 150 diseases, including certain forms of cancer, diabetes, infertility, myopathies, and neurodegenerative diseases, are caused by defective mtDNA; and approximately one out of every 200 children is born with mitochondrial mutations.

To correct this situation, investigators from the Oregon Health & Science University (Beaverton, USA) worked with monkeys as a model of human inherited mitochondrial disease. They reported in the August 26, 2009, online edition of the journal Nature that by employing a technique called spindle replacement they could remove the genetic material from an egg with mutated mtDNA and transfer it to an enucleated egg with healthy mtDNA.

The experiment was performed using eggs from two different monkeys. After transfer of the genetic material, the reconstructed eggs with the mitochondrial replacement were capable of supporting normal fertilization, embryo development, and produced healthy offspring. DNA screening studies of the baby monkeys that developed from the reconstructed eggs showed that they were genetically the offspring of the egg donor, but that their mitochondria were from the enucleated egg. No mtDNA from the donor egg could be detected in the offspring.

"In theory, this research has demonstrated that it is possible to use this therapy in mothers carrying mitochondrial DNA diseases so that we can prevent those diseases from being passed on to their offspring,” said senior author Dr. Shoukhrat Mitalipov, assistant scientist in reproductive biology at the Oregon Health and Science University. "We believe that with the proper governmental approvals, our work can rapidly be translated into clinical trials for humans, and, eventually, approved therapies.”

Related Links:
Oregon Health & Science University