Stem cell therapy for MS seen to lower mitochondrial DNA in study
High levels found in MS patients may contribute to inflammatory processes
People with multiple sclerosis (MS) have higher amounts of mitochondrial DNA in their spinal fluid, which surrounds the brain and spinal cord, than do their healthy counterparts, a small study found.
Mitochondria are small cellular organelles that produce most of the energy needed to power cells. These cell powerhouses have their own DNA, which can be released into the surrounding fluid and contribute to inflammatory processes.
In this study, however, researchers also observed that treatment with stem cell therapy brought mitochondrial DNA to near-normal levels, suggesting it could be a marker of disease activity and response to treatment for MS.
The study, “Cerebrospinal fluid mtDNA concentrations are increased in multiple sclerosis and were normalized after intervention with autologous hematopoietic stem cell transplantation,” was published in Multiple Sclerosis and Related Disorders.
Stem cell therapy for MS found to normalize mtDNA concentrations
MS occurs when healthy parts of the brain and spinal cord become inflamed and damaged, causing a range of symptoms. It is thought that certain immune cells in MS may go haywire and burst open, releasing DNA from their mitochondria that boosts further inflammatory processes.
Earlier work has suggested that changes in mitochondria occur early in the disease course and contribute to neurodegeneration. However, treatment with certain disease-modifying therapies seems to reduce the amount of mitochondrial DNA — known as mtDNA — that gets released into the cerebrospinal fluid, or CSF.
Now, researchers in Sweden conducted a study involving MS patients and healthy people. There were two main goals: First, to determine if MS patients indeed have higher levels of mitochondrial DNA in the CSF than do healthy controls, and second, to investigate if treatment with a stem cell transplant could lower the levels of that DNA in patients. Such a transplant, known as autologous hematopoietic stem cell transplantation (aHSCT), uses cells collected from the patient.
The study included 48 people with relapsing-remitting MS and 32 healthy individuals. The results showed that the MS patients had significantly more copies of mtDNA than did the healthy individuals (a median of 16 vs. 5.6 copies per microliter of CSF).
The amount of mtDNA was not impacted by sex or age in either group, but correlated with the number of relapses, disability levels, and a shorter disease duration in patients. Levels of mtDNA also were linked with higher the levels of neurofilament light chain (NfL), a marker of nerve cell damage, and a higher number of lesions with active inflammation.
All patients planned to undergo a stem cell transplant, a procedure that aims to reset the immune system. It involves collecting a patient’s own hematopoietic stem cells — immature cells that can develop into all types of blood cells — then wiping out the entire immune system with a round of chemotherapy or radiation therapy, and infusing the stem cells back to give rise to new immune cells.
By generating immune cells that are not primed to attack the brain and spinal cord, the procedure is expected to reduce the inflammation and nerve cell death that drives MS.
One year after the transplant, the results showed, the median number of mtDNA copies decreased significantly, from 16 to 5.9 copies per microliter. That number remained significantly reduced in the years that followed, at 8 copies per microliter after two years, and 7.2 copies per microliter after 3-5 years.
“mtDNA concentrations were normalized in MS patients after intervention with aHSCT,” the researchers wrote.
After the transplant, a total of 39 patients retained a status called no evidence of disease activity (NEDA-2), meaning they experienced no new MRI activity and no relapses over the follow-up period. The other nine patients had evidence of inflammatory disease activity (EIDA), and had experienced at least one of these events.
Data showed that patients with EIDA had significantly higher levels of mtDNA one year after the transplant that those with NEDA-2 (10 vs. 5.2 copies per microliter). The difference remained significant after two years (18 vs. 7.1 copies per microliter), but not after 3-5 years.
“These results position mtDNA as a potential biomarker for monitoring inflammatory activity and response to treatment in MS,” the researchers wrote. In addition, “our study adds to the growing evidence base for the therapeutic efficacy of aHSCT.”
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