Babies born with incurable inherited diseases could soon have damaged organs restored through stem-cell treatment

Babies born with incurable inherited diseases might in the future be able to undergo a revolutionary stem-cell treatment that restores the function of at least some of their damaged organs and tissues, scientists have said.

A study into mitochondrial diseases, which are maternally inherited, has shown for the first time that it is possible to produce healthy stem cells that are free of genetic mutations by engineering the skin cells of an affected patient.

The idea, eventually, is to generate enough healthy stem cells from a patient’s skin that can then be transplanted back into the patient’s own body to repair defective organs – such as heart, eyes or muscles – damaged by the mitochondrial mutations inherited from the mother.

At present there are no effective treatments for the scores of diseases caused by mutations in the DNA of the mitochondria, the tiny “organelles” of the cell that are responsible for converting energy from food into the useable chemical energy of the body.

However, the scientists behind the research believe that the new approach now opens the way to developing stem-cell treatments that restore the energy supply to the most affected tissues, leading to new therapies and possibly even cures.

“To families with a loved-one born with a mitochondrial disease waiting for a cure, today we can say that a cure is on the horizon,” said Shoukhrat Mitalipov of the Oregon Health and Science University in Portland, Oregon, who led the study published in the journal Nature.

“Over the past several years, we have been working to generate stem cells for use in combating disease. This critical first step toward treating these diseases using gene therapy will put us on the path to curing them,” Dr Mitalipov said.

“And, unlike unmatched tissue or organ donations, combined gene and cell therapy will allow us to create the patients’ own healthy tissue that will not be rejected by their bodies,” he said.

The prospects of a cure for mitochondrial diseases are, however, a long way off and some other experts familiar with the work said that it remains highly experimental and too complicated and costly to attempt human clinical trials at this stage.

“Given the complexity of the technology, costs and risks involved, the strategies described here will remain a proof-of-concept and unlikely see a practical use in clinical medicine,” said Dusko Ilic, a stem-cell expert at King’s College London, who was not involved with the research.

Nevertheless, the study is seen as an important breakthrough in the fundamental understanding and possible treatment of diseases that can be severely debilitating for the children and adults with mitochondrial defects.

Until now, scientists have concentrated on ways of eliminating the mitochondrial defects in fertilised egg cells as a way of avoiding passing on the mutations in a new form of IVF treatment that has only recently been approved in the UK.

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However, Dr Mitalipov’s team has shown that stem-cell therapies may in the future be possible through one of two different approaches: either by generating healthy stem cells directly from a patient’s skin cells after a form of genetic screening, or by creating embryonic stem cells using the egg cell of a healthy mitochondrial donor.

“This study is actually about coming up with stem cells that can be used for gene therapy,” Dr Mitalipov told The Independent.

“For patients with mitochondrial disease there are no treatments, so cell-replacement therapy may be the most appropriate, particularly as some tissues and organs are affected by the inability to produce energy,” he said.

“Both approaches for full reprogramming work well and the cells that we select have no mutations and indeed recover their ability to produce energy.

“We’ve done extensive tests in Petri dishes in vitro by differentiating them into cardiac cells, into muscle cells, into neurons and then measuring their ability to produce energy. They are actually normal as this stage,” Dr Mitalipov explained.

Some mitochondrial diseases will be easier to treat by this technique than others. One condition for instance, called Liber disease, mainly affects the eyes, which means it is suitable for stem-cell therapy, he said.

“The prospects are very difficult for some mitochondrial disease because many organs are affected,” Dr Mitalipov said.

“We hope that we will use a non-human primate model to develop this approach to replace diseased tissue in organs and hopefully that will help us to move quickly to human clinical trials,” he said.

Other researchers warned that this is likely to take many years and it is a “leap of faith” to assume that the corrected stem cells can be used to treat or cure a mitochondrial-disease patient.

“There are, however, many hurdles before that can be achieved, some of which may be difficult if not impossible to cross,” said David Valle of the Johns Hopkins School of Medicine.

Mitochondria are the tiny “power packs” of cells and their job is to convert the energy of glucose, derived from food, into the chemical energy “currency” ATP.

If this vital function of the mitochondria is damaged, it results in a wide range of symptoms connected with lack of energy, such as poor growth, loss of muscle function, visual problems, learning disabilities, heart, liver and kidney disease, and neurological problems including dementia.

Illnesses caused by inherited mitochondrial disease include: Leigh syndrome, which causes a rapid decline in health after the first year of life; Leber’s disease, which causes loss of vision; and MELAS syndrome, a collection of symptoms caused by mitochondrial defects.

There are many inherited diseases associated with defective mitochondria.