In lab, progress in fixing a source of genetic disease

Scientists on Wednesday reported that, in pioneering experiments on human eggs, they had replaced a genetic mechanism blamed for crippling diseases. The laboratory breakthrough could one day lead to human trials to avert so-called mitochondrial disorders, they said. Other experts praised the work but sounded caution. Described in the journal Nature, the research aims at sidestepping genetic defects handed down by the maternal line through cellular mechanisms known as mitochondria. These are tiny structures that convert fats and sugars to energy for the cell. They only carry a few dozen genes, or about 0.1 percent of the DNA code, and are separate from the nucleus of the cell which contains the remainder. However, when mitochondrial genes carry a defect, the impact on health can be huge. Eye disorders, cardiac malfunction, diabetes, gastrointestinal and muscular diseases and even kinds of dementia can result. A team led by Shoukhrat Mitalipov at the Oregon Health and Science University in Portland, Oregon, said they had reached a milestone in years-long research to replace faulty mitochondria. The idea is to take the nucleus of the mother's egg at a stage when the chromosomes are lined up in a structure called a spindle. The mitochondria in the maternal egg is left behind and the egg discarded. The spindle is then placed in a donor's egg whose nucleus has been removed, but whose mitochondria is normal and remains in place. Thus reconstructed -- consisting of the mother's DNA and the donor's healthy mitochondria -- the egg is fertilised with sperm from the intended father, using in-vitro technology. Mitalipov obtained 106 human eggs from seven volunteers and carried out experiments to see if the spindle switch would work. After fertilisation, manipulated eggs were allowed to develop into clusters of very early-stage embryos, comprising clusters of 100 cells. "We have shown that mutated DNA from the mitochondria can be replaced with healthy copies in human cells," Mitalipov said in a press release. "This research shows that this gene therapy method may well be a viable alternative for preventing devastating diseases passed from mother to infant." His team also reported a success in testing the technique on animal primates. They thawed the frozen egg of a macaque and switched the nuclear spindle. The embryonic cells were implanted in a female monkey and resulted in a healthy baby dubbed Chrysta. That experiment is important, said Mitalipov. If ever mitochondrial therapy is authorised, preservation of the egg through freezing may well be essential so that both the donor egg and the mother's egg are available at the same time. Other specialists said the research was encouraging but added many hurdles remained. Only 43 percent of the manipulated eggs developed to a healthy embryonic stage where, in theory, they could be implanted, they noted. This disappointingly low success rate points to problems in manipulating human eggs, they said. "This is excellent and important work... however, it is still a long way off for human use," Peter Braude, a professor of obstetrics and gynaecology at King's College London, told Britain's Science Media Centre. According to a "conservative" 2010 estimate by Patrick Chinnery, a geneticist at Britain's Newcastle University, mitochondrial disease occurs in more than one in 10,000 people.