Their mother's gift may re-energize the cells of children carrying defective mitochondria as organelles
for cellular powerhouses.
A team of researchers is testing a strategy to soak a patient's blood cells in a "nourishing soup" of the mother's healthy mitochondria before reinfusing them
.
Early indications are that the intervention is safe and may improve children's health and development, and researchers are planning a follow-up clinical trial
.
Mary Kay Koenig, a pediatric neurologist at the University of Texas Health Sciences Center in Houston, said the approach is "different from what others do," and she has nothing to do with the study, which was published today Science Translational Medicine
。 She said that while the results are still in their early stages, they are "very exciting.
"
But Michael Hannah, a clinical neurologist at the Queens Square Institute of Neurology at University College London, believes that "caution is important
.
" This is highly preliminary data
.
”
Mitochondria originated early in eukaryotic evolution as a commensal bacterium in other organisms that produced adenosine triphosphate (ATP),
which mostly fuels cells.
But about one in every 5,000 babies is born with mitochondrial defects, which can sometimes lead to fatal diseases
.
Elad Jacoby, a pediatric hematologist and oncologist at Sheba Medical Center, and colleagues knew that when isolated mitochondria mix with cells, organelles slide into the cells and start working
.
Koenigbi and colleagues realized that they might be able to use this behavior to increase the number of
healthy mitochondria in a patient's cells.
The team decided to target hematopoietic stem cells and progenitor cells (HSPCs), stem cells found in bone marrow capable of producing a series of blood cells
.
Jacoby said heat shock proteins are also found throughout the body and may inhibit the effects of disease in
other tissues.
Using compassionately, the researchers studied 6 children with Pearson syndrome or Kearns-Sayre syndrome (a disease caused by a deletion of mitochondrial DNA), a regulatory pathway
to test experimental methods in people with incurable diseases.
Koenig said the children's cells "work on low power," leading to problems such as
kidney disease, diabetes, arrhythmias and weakness.
Growth disorders make them shorter
than 97% of their peers.
The researchers extracted healthy mitochondria from the mother's blood and mixed
it with the patients' HSPCs.
"You put them in a test tube, shake them, and leave them for a while
," Koenig said.
The team returned the cells to the patient's bloodstream
after 24 hours of culture.
Mitochondrial activity in cells suggests that at least some of these cells take up organelles
.
One year after the transfusion, the amount of mitochondrial DNA in the patient's blood cells increased by 30 percent, and the production of ATP increased by a third
.
Five of the children gained weight, and strength and endurance tests showed improvement
in two patients.
The team reports that all are still alive, including a child
who received treatment nearly 5 years ago.
Koenig said she was encouraged
by the fact that "they are showing some improvement.
" But she cautioned that it would be difficult
to confirm that treatment was responsible.
The study did not have a control group to compare, and scientists don't know how the symptoms of these diseases typically evolve as children age
.
Still, Koenig said, "we (usually) expect every patient's condition to decline
.
" ”
They suspect that mitochondrially healthy heat shock protein cells have a big impact outside the blood, because mitochondrial defective cells far outweigh them
.
The researchers and a company they founded to commercialize their work is currently analyzing the results of a clinical trial on five other patients with both syndromes, and plans to start another trial to determine if the reperfused cells can stabilize and survive
.
If further research confirms this benefit, Koenig said, "this could be effective
for a whole host of mitochondrial diseases.
" ”
