New study shows how mitochondrial disease may be prevented

A joint team of scientists from The New York Stem Cell Foundation (NYSCF) Laboratory and Columbia University Medical Center (CUMC) has developed a technique that may prevent the inheritance of mitochondrial diseases in children. The study is published online today in Nature.

Dieter Egli, PhD, and Daniel Paull, PhD, of the NYSCF Laboratory with Mark Sauer, MD, and Michio Hirano, MD, of CUMC demonstrated how the nucleus of a cell can be successfully transferred between cells. This landmark achievement carries significant implications for those children who have the potential to inherit .

Mitochondria are cellular organelles responsible for the maintenance and growth of a cell. They contain their own set of genes, passed from mother to child, and are inherited independently from the cell's nucleus. Although accounts for only 37 out of more than 20,000 genes in an individual, mutations to carry harmful effects.

Mitochondrial disorders, due to mutations in mitochondrial DNA, affect approximately 1 in 10,000 people, while nearly 1 in 200 individuals carries mutant mitochondrial DNA. Symptoms, manifesting most often in childhood, may lead to stunted growth, , muscle weakness, neurological disorders, loss of vision and hearing, and respiratory problems, among others. Worldwide, a child is born with a mitochondrial disease approximately every 30 minutes, and there are currently no cures for these devastating diseases.

"Through this study, we have shown that it should be possible to prevent the inheritance of mitochondrial disorders," said Egli, PhD, co-author of the study and an Senior Researcher in the NYSCF Laboratory. "We hope that this technique can be advanced quickly toward the clinic where studies in humans can show how the use of this process could help to prevent mitochondrial disease."

In this study, the researchers removed the nucleus of an unfertilized egg cell and replaced it with the nucleus of another donor's egg cell. The resultant egg cell contained the genome of the donor but not her mitochondrial DNA. The researchers demonstrated that the transfer did not have detectable adverse effects on the egg cell, a prerequisite for clinical translation. They achieved this by lowering the temperature of the egg before nuclear transfer, a novel technique. Previous studies report adverse consequences in approximately 50% of the egg cells.

The researchers then artificially activated the egg cell through a technique called parthenogenesis and derived stem cell lines from the blastocyst that developed. These cell lines were grown for more than a year and generated adult cell types such as neurons, heart cells and pancreatic beta cells that are affected by mutant mitochondrial DNA. They found the levels of the donated genome's original mitochondria to be undetectable, demonstrating that this would permanently eliminate the mitochondrial DNA and prevent a family's future generations from developing these diseases.

Current treatment options to prevent mitochondrial disease are limited. A woman with a family history of mitochondrial disease may abstain from having children. She may alternatively elect to undergo in vitro fertilization (IVF) with donor eggs; however, this means the child will be genetically unrelated to her. As another option, patients can undergo IVF treatment and, through prenatal screening, to allow clinicians to select from a mother's eggs those that have the least likelihood of carrying mitochondrial DNA defects. This is not, however, a fully effective screening process, and her children may still be affected by mitochondrial disorders.

"Women who carry mutant mitochondrial DNA may no longer have to worry that their children will become sick. This technique may allow us to provide women with a therapeutic option that will prevent these disorders," said Sauer, MD, a co-author on the paper and Vice Chairman of the Department of Obstetrics and Gynecology and Chief of Reproductive Endocrinology at Columbia University Medical Center. Sauer is also Program Director of Assisted Reproduction at the Center for Women's Reproductive Care.

"These findings epitomize the goals and aspirations of The New York Stem Cell Foundation – to accelerate and find cures, and prevent diseases," said Susan L. Solomon, CEO of The New York Stem Cell Foundation. "This research underscores the importance of interdisciplinary collaborations in which close partnerships between researchers and clinicians allow for tremendous advances that previously were not possible."

"We often know too late that a patient runs the risk of passing on defective mitochondria to her children. It is absolutely devastating to a patient and her family," said Hirano, MD, Professor of Neurology and Co-Director of the Adult Muscular Dystrophy Association clinic at Columbia University Medical Center, where he sees patients with mitochondrial disease. "This new technique offers an effective solution by ensuring only healthy mitochondria are present in the egg cells."

The scientists plan to move toward clinical application using this technique. Next steps include the production of more mitochondrial disease-free and the generation of healthy progeny in an animal model.

Related Stories

Researchers test new gene therapy method in human cells

Oct 24, 2012

Oregon Health & Science University's development of a new gene therapy method to prevent certain inherited diseases has reached a significant milestone. Researchers at the university's Oregon National Primate Research Center ...

Recommended for you

Scientists image a beating heart in 3D (w/ Video)

1 hour ago

Researchers of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden report how they managed to capture detailed three-dimensional images of cardiac dynamics in zebrafish. The novel approach: ...

New device to monitor lung function in space

1 hour ago

A new method of collecting blood from the ear, currently part of an interactive exhibition at the Science Museum, could be used to monitor lung function in space. Less invasive, faster and more accurate than current methods, ...

Primate research center plays key role in HIV study in Nature

1 hour ago

In a study reported in Nature this month, Yerkes National Primate Research Center researchers were key in determining that treating SIV-infected rhesus macaques with type 1 interferon, a protein known to trigger antiviral respon ...

Three-people IVF debate process on the move in UK

4 hours ago

Takes two to make a child, correct? No. maybe. The use of sperm and eggs from three people to create babies moved a step closer in the UK, with Tuesday's events. What kind of egg-sperm distribution are we talking about? The ...

User comments