A gift from their mothers might reenergize the cells of children who carry faulty mitochondria, the organelles that serve as cells’ power plants. A research team is testing a strategy that involves soaking patients’ blood cells in a broth of healthy mitochondria from their mothers and then reinfusing them. Early signs suggest the intervention is safe and may improve the children’s health and development, and the researchers are planning a follow-up clinical trial.
This approach “is different from what anyone else is doing,” says Mary Kay Koenig, a pediatric neurologist at the University of Texas Health Science Center, Houston, who wasn’t connected to the study, published today in Science Translational Medicine. Although the results are at a very early stage, they are “very exciting,” she says. But Michael Hanna, a clinical neurologist at the University College London Queen Square Institute of Neurology, believes “it’s important to be cautious. This is highly preliminary data.”
Mitochondria, which originated early in eukaryotic evolution as symbiotic bacteria within other organisms, generate most of the adenosine triphosphate (ATP) that fuels cells. But about one in 5000 babies is born with mitochondrial defects that cause sometimeslethal disorders.
Elad Jacoby, a pediatric hematology and oncology physician at Sheba Medical Center, and colleagues knew that when isolated mitochondria are mixed with cells, the organelles slip into the cells and start working. Jacoby and colleagues realized they might be able to harness this behavior to boost the number of healthy mitochondria in patients’ cells.
The team decided to target hematopoietic stem and progenitor cells (HSPCs), stem cells found in bone marrow that give rise to a range of blood cells. HSPCs also disperse throughout the body and may suppress disease effects in other tissues, Jacoby says.
Under compassionate use, a regulatory path for testing experimental approaches in people with untreatable illnesses, the researchers studied six children with Pearson syndrome or Kearns-Sayre syndrome, conditions caused by a missing chunk of mitochondrial DNA. The children’s cells “were working on low battery,” Jacoby says, resulting in problems such as kidney disease, diabetes, abnormal heart rhythms, and weakness. Impaired growth had left them shorter than about 97% of their peers.
The researchers extracted healthy mitochondria from the mothers’ blood and HSPCs from the patients, then mixed them. “You put them in a tube, shake it, and leave it for a while,” Jacoby says. The team returned the cells to the patients’ bloodstream after 24 hours of incubation.
Mitochondrial activity in the cells suggested at least some of them had absorbed the organelles. A year after reinfusion, the patients’ blood cells held 30% more mitochondrial DNA and produced one-third more ATP than before. Five of the children gained weight, and two patients tested for strength and endurance showed improvements. All are still alive, including one child who underwent the treatment nearly 5 years ago, the team reported.
Koenig says she is encouraged by “the fact that they are showing some improvements.” But confirming the treatment was responsible is difficult, she cautions. The study did not have a control group for comparison, and scientists don’t understand how the symptoms of the diseases typically evolve as children age. Still, Koenig says, “We [normally] expect every patient to decline.”
Hanna, however, says he doubts HSPCs with healthy mitochondria would have much of an impact outside the blood because they would be vastly outnumbered by cells with faulty mitochondria.
The researchers and a company they have founded to commercialize their work are now analyzing results from a clinical trial of the treatment on five more patients with the two syndromes and plan to start another trial that will try to establish that the reinfused cells settle down and survive. If further research confirms the benefits, Koenig says, “There’s a whole bunch of mitochondrial disorders this could work for.”
Mitch Leslie writes about cell biology and immunology.
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