Antibodies in spinal fluid seen to drive PPMS, but not relapsing MS
by Marisa Wexler, MS | February 7, 2023 – MS News Today
artwork by MS Views and News
Primary progressive multiple sclerosis (PPMS) is driven by antibodies in the cerebrospinal fluid (CSF), the liquid around the brain and spinal cord — but this is not the case in the more common relapsing forms of MS — a new study done in mice suggests.
Researchers say this result will have far-reaching impact in the treatment of PPMS versus other types of multiple sclerosis.
“By developing an animal model specifically designed for PPMS, our team has been able to at long last confirm a widely-suspected hypothesis: that PPMS is in fact its own disease,” Saud A. Sadiq, MD,a neurologist from the Tisch MS Research Center of New York and co-author of the study, said in a Tisch press release.
“This finding not only gives us the ability to conduct more precise research on PPMS and develop more targeted treatments — but it also represents another important step toward our center’s overarching goal to find the cause of and the cure for MS,” Sadiq added.
The study, “Cerebrospinal fluid immunoglobulins in primary progressive multiple sclerosis are pathogenic,” was published in Brain.
Finding may lead to new strategy to treat primary progressive MS
According to the research team, this finding lends credence to the idea of advancing CSF pheresis — using a machine to filter out the CSF, similar to how dialysis is used to filter blood — as a potential treatment strategy in primary progressive MS.
“For thousands of PPMS patients and their families, who have long been without effective treatment options, this research is potentially game-changing,” said Jamie Wong, PhD, a researcher at Tisch and study lead author.
Most people with MS initially develop relapsing-remitting disease, characterized by relapses in which symptoms suddenly worsen followed by periods of remission where symptoms ease or disappear entirely. About 10% of MS patients will instead develop PPMS, where symptoms continually worsen over time immediately from onset.
While the terms “primary progressive” and “relapsing” are commonly used to describe the clinical course of MS, it has not been clear whether these two conditions are spectrums of the same disease or distinct clinical entities.
Now, scientists conducted a straightforward test in which they collected cerebrospinal fluid, known as CSF, from 42 people with MS. The CSF is the liquid that surrounds the brain and spinal cord. This study involved 17 patients with PPMS, 13 with relapsing-remitting MS, and 12 with secondary progressive MS.
After its collection, the CSF was injected into the space around the spinal cord of mice.
“Our animal model relies on direct transmission of disease pathology using CSF from MS patients, which arguably mimics [disease] mechanisms occurring in patients with greater specificity than any currently existing animal model of MS,” the scientists wrote.
The results showed that mice injected with CSF from PPMS patients started to exhibit motor symptoms, such as reduced grip strength and limp tails. Tissue analyses showed these mice also had regions of damage to myelin, the fatty sheath around nerve fibers that is progressively lost in MS, with strong pro-inflammatory activation of nervous system support cells.
All in all, the clinical picture of these mice was very similar to MS, the researchers noted.
By comparison, mice injected with CSF from patients with relapsing forms of disease did not develop motor symptoms or show signs of myelin damage.
“The motor impairments and [tissue] changes observed only in spinal cords of PPMS CSF-injected mice suggest that the pathogenic [disease-driving] capacity of CSF is unique to PPMS,” the researchers wrote. They noted, however, that “this does not exclude the possibility that other shared non-CSF-mediated pathological mechanisms exist between PPMS” and other MS types.
Data show unique driver of primary progressive MS
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