Twin monkeys born in a breakthrough experiment conducted in the US could open the way to a new gene therapy that uses a fertility method called spindle transfer to transplant DNA from one egg to another to prevent certain types of inherited diseases passing from mother to offspring.

The twin monkeys called “Mito” and “Tracker” are the world’s first animals to be born after using spindle transfer. The breakthrough experiment was the work of researchers at the Oregon Health & Science University’s (OHSU) Oregon National Primate Research Center (ONPRC), and is described in a paper that appeared online the journal Nature on 26 August.

This successful result opens the way to a new type of fertility method that could healp break the chain of several serious genetic diseases that are passed from mothers to their offspring through mutated DNA in the mother’s cell mitochondria.

One of the authors, Dr Shoukhrat Mitalipov, told the media that:

“We believe this discovery in nonhuman primates can rapidly be translated into human therapies aimed at preventing inherited disorders passed from mothers to their children through the mitochondrial DNA, such as certain forms of cancer, diabetes, infertility, myopathies and neurodegenerative diseases.”

Mitalipov, who is an associate scientist in the Division of Reproductive Sciences at ONPRC, the Oregon Stem Cell Center and the departments of Obstetrics and Gynecology and Molecular & Medical Genetics of Oregon Health & Science University (OHSU), explained that:

“Currently there are 150 known diseases caused by mutations of the mitochondrial DNA, and approximately 1 out of every 200 children is born with mitochondrial mutations.”

Mitochondria are like little power plants inside each cell: they provide the energy that the cell needs to grow and metabolize, and they also have their own DNA that is separate from the DNA in the nucleus.

When sperm fertilizes an egg cell, the resulting embryo almost always inherits its mitochondria from the egg, which carries only the mother’s mitchondrial DNA, and if she carries mitchondrial mutations that cause disease, then so will the embryo.

For the study, Mitalipov and colleagues used a fertility method they developed called spindle transfer, where they transfer the chromosomes of the mother (leaving behind her mitochondrial DNA) into a healthy donated egg that has been stripped of its chromosomes but not its healthy mitchondrial DNA.

The new egg is then fertilized and develops into an embryo made with the DNA of the mother and the father, but without the mitchondrial DNA of the mother, instead the it inherits the mitochondrial DNA of the donor of the egg.

In this case, the researchers implanted the fertilized monkey embryos into surrogate mothers that went on to give birth to two healthy twin monkeys, nicknamed “Mito” and “Tracker”, after the procedure that was used for imaging the mitochondria.

(Note the monkeys were twins because the egg and sperm they were made from came from the same parents although they were born to different surrogate mothers).

Follow up tests found little to no trace of cross-animal mitochondrial transfer, showing that the experiment succeeding in keeping nuclear genetic material separate from mitochondrial genetic material during the transfer.

Mitalipov said that in theory he and his colleagues had established that it was possible to use this approach to help mothers carrying mitochondrial DNA diseases from passing them onto their children.

“We believe that with the proper governmental approvals, our work can rapidly be translated into clinical trials for humans, and, eventually, approved therapies,” he added.

The Oregon National Primate Research Center, the Oregon Stem Cell Center; and the National Center for Research Resources and the National Institute of Child Health and Human Development, both components of the National Institutes of Health, paid for the study.

“Mitochondrial gene replacement in primate offspring and embryonic stem cells.”
Masahito Tachibana, Michelle Sparman, Hathaitip Sritanaudomchai, Hong Ma, Lisa Clepper, Joy Woodward, Ying Li, Cathy Ramsey, Olena Kolotushkina, Shoukhrat Mitalipov.
Nature, 26 August 2009
DOI: 10.1038/nature08368

Source: OHSU Primate Center.

Written by: Catharine Paddock, PhD