Mitochondrial transplantation appears safe in children with rare diseases

An innovative therapy aiming to treat mitochondrial disease has shown encouraging results in six children.

Doctors at Sheba Medical Centre, Tel Aviv, Israel, transplanted healthy mitochondria, donated by the children's mothers, through a compassionate use programme. The results, published in Science Translational Medicine, suggest that the procedure is safe and some improvements were observed in the children's health.

'These are very soft measures that are hard to report, but we did see major improvements to the quality of life in almost all of these children,' commented lead author Dr Elad Jacoby.

Mitochondria provide the energy needed to fuel biological processes at a cellular level. They are a special type of organelle (mini structures within the cell), as they have their own DNA called mitochondrial DNA (mtDNA). Mutations in mtDNA can cause defects that can have a substantial, negative impact on the functioning of mitochondria and therefore the cell. As a result, mitochondrial disease can cause a variety of disorders affecting many organs, including the brain, muscles, heart, and eyes.

The children involved in this clinical trial had either Pearson syndrome or Kearns-Sayre syndrome, with symptoms including kidney disease, diabetes, abnormal heart rhythms, and weakness. Both are caused by single large-scale mitochondrial DNA deletions, and no disease modifying therapies are currently available.

In an attempt to treat them, mitochondria were extracted from the mothers' blood, then mixed with haematopoietic stem cells, found in the bone marrow from the child before being returned to their blood. The procedure relies on a natural process where the haematopoietic stem cells take up the mitochondria. 'You put them in a tube, shake it, and leave it for a while,' said Dr Jacoby.

After six-12 months, the children had higher levels of mtDNA in their blood, five out of six had increased their bodyweight, and all had improvements in quality-of-life measurements.

Dr James McCully, a cardiac surgeon at Boston Children's Hospital, who was not involved in the trial, commented: 'this is a good first study to show that mitochondrial transplantation is safe in patients with these gene deletion disorders.'

Although these are promising results, they are very preliminary data and should be interpreted with caution. However, the researchers are continuing their work and are currently analysing results from a clinical trial (NCT03384420) with a further five patients. If this therapy proves successful it could be beneficial for the treatment of many mitochondrial diseases.