Reprogrammed stem cells of people without MS seem to better protect the brain.
Research from the University of Connecticut suggested that the reprogrammed stem cells of people with Primary Progressive Multiple Sclerosis (PPMS) don’t protect the brain as well as reprogrammed stem cells from patients without multiple sclerosis.
The study further showed that the effiacy of PPMS therapies could vary greatly from patient to patient. The researchers believed this insight might help drug developers more accurately ascertain whether, and on which patients, new and existing therapies are effective.
The study was led by Stephen Crocker, PhD (pictured), an associate professor of neuroscience at UConn. He and his colleagues wanted to understand why so many MS drugs seemed to fail in patients despite success in a laboratory setting.
To investigate the question, Crocker and his team looked at neural progenitor cells, which are found in lesions in PPMS patients and are believed to influence oligodendrocyte progenitor cell maturation. The team collected blood samples from MS patients and from close relatives or spouses who did not have MS. From those blood samples, the researchers created induced pluripotent cells (iPS), which they used to compare neural progenitor cells of MS patients to non-MS patients.
Scientists noted a clear divergence when the stem cells were implanted in animals with MS-like defects. Stem cells from non-MS patients seemed to spark cellular repair in the subjects. However, no such improvement was found when the stem cells of PPMS patients were implanted in the animals.
“It’s like you bring in the National Guard to stem a riot, and [instead] they all sit down and start having lunch,” said Crocker, in a press release.
The researchers also looked at the conditioned media in which the stem cells were grown.
They wondered if the proteins and other chemicals left behind might have an impact on young oligodendrocytes. Once again, a stark difference emerged.
In media conditioned by healthy patients’ stem cells, the oligodendrocyte cells grew into normal, healthy cells. In the media conditioned by PPMS patients’ stem cells, the oligodendrocytes failed to mature.
The scientists found similar results when they tested the effect of several PPMS drug candidates on young oligodendrocyte cells that were grown in conditioned media. Those grown in the conditioned media of healthy patients responded positively to the drug candidates.
However, when the therapies were tested on oligodendrocytes grown in PPMS patients’ conditioned media, the results varied. In other words, it wasn’t that the drug candidates worked or didn’t work; it depended on the individual patient.
The researchers believed these deviations may be due to variances in the actual disease of PPMS patients. These minor disease differences could be why some drugs work in the lab but seem to fail in many patients in the real world. The researchers said their study could also provide a pathway by which therapies could be tested in advance to see which are most likely to work on an individual patient.
The study, titled “iPS-derived Neural Progenitor Cells from PPMS Patients Reveal Defect in Myelin Injury Response,” was published in February in Experimental Neurology.