A technique that could allow women with mitochondrial diseases to have healthy children showed promise in a group of four women — and the research also flagged why it might not work in some cases.
Why it matters:
Mitochondrial diseases are transmitted from mothers to their offspring; they have no cures and are often fatal. But an experimental therapy has shown promise in animals, and one boy was born this spring in Mexico with the technique.
The approach involves taking the nucleus out of a donor egg that has healthy mitochondria and replacing it with the nucleus from the mother with the mitochondrial disease. But when you suck that nuclear DNA out of the mother’s egg, a little bit of diseased mitochondria might come along for the ride, and scientists want to know whether those mitochondria will hijack the new egg and give the child the disease.
While the technique had been studied in healthy human cells before, this was the first paper that used eggs from women that had mitochondrial diseases, said Dr. Paula Amato, a coauthor and OB-GYN at Oregon Health and Science University.
The scientists studied eggs from four women with mitochondrial disease and 11 healthy women. They transferred nuclear DNA from the cells with diseased mitochondria into the donor cells and then formed “cell lines” — collections of identical cells derived from a single cell. (They also made cell lines by transferring nuclear DNA from healthy cells to other healthy cells, for controls.) Then they cultured the cells for up to 10 weeks and found that the majority of cell lines had less than 1 percent of the diseased mitochondrial DNA — a good sign. But in two of the cell lines, the diseased mitochondria took over, erasing any trace of their healthy counterparts. In other words, the cells “reversed” to a diseased state. (A similar process happened for two of the control cell lines.)
That aligns with research published earlier this year, but it goes a step further, identifying particular genetic characteristics of the reversed cell lines that might explain why, in those cell lines, the defective mitochondria took over. The researchers said that could someday enable a system to match mothers to donors.
But keep in mind:
“The phenomenon we see is still purely artificial,” said Shoukhrat Mitalipov, director of the OHSU Center for Embryonic Cell and Gene Therapy — meaning that the diseased mitochondria taking over the cell only happens in the cell cultures in a lab, and not necessarily in real animals. His lab has produced rhesus macaques and mice using this technique, and in none of the animals does the original mother’s mitochondria take over the cell.
It’s also a small sample size. In a clinical trial, Mitalipov would like to recruit 10 or 15 women with mitochondrial disease, but since he had to rely completely on private funding for this study, he set the limit at five. (One dropped out when she was later determined to be ineligible.)
What they’re saying:
“I think this paper clearly is an another move forward in buttressing the body of science [of mitochondrial replacement therapy],” said Dr. Eli Adashi, a professor of medical science at Brown University’s Warren Alpert Medical School who has written articles about the politics of such therapies. But it will be hard for researchers to take full advantage of that science, he said, if the government continues to prohibit federal dollars from being spent on it.
The bottom line:
Understanding why some mitochondrial replacements work while others don’t is one of the next stages of translating this promising therapy to the clinic.