Multiple sclerosis (MS) has been studied extensively, and its more severe, rare form has long been believed by clinicians and researchers to be its own illness. A recent study utilizing a more precise mouse model has now verified this suspicion.
The first mouse model of primary progressive multiple sclerosis (PPMS) was produced by researchers at New York’s Tisch MS Research Center and published on February 3 in Brain. The model demonstrated that PPMS had a separate pathology from other forms of MS.
The concept and the findings of the researchers make it clear that PPMS has to be investigated independently of other MS varieties like secondary progressive MS (SPMS), and it may also lead to the discovery of innovative treatment approaches.
“In a lot of the studies that have been performed, researchers lump secondary and primary progressive MS into one category,” said lead author Jamie Wong in an interview. “Moving forward, based on these results, I think people should be more aware of these differences between primary progressive MS and secondary progressive MS and really try to focus on treating these as two distinct entities.”
Somewhere between 10% and 15% of MS patients are also diganosed with PPMS. After the onset of symptoms, there is no respite from PPMS, unlike the most frequent kind, relapsing-remitting MS. Furthermore, PPMS is a new diagnosis, as opposed to SPMS, which develops after years of RRMS.
PPMS is unique among MS subtypes in both its symptoms and its pathogenesis. For instance, compared to individuals with RRMS, those with PPMS are more likely to experience sensory issues like weakness. Moreover, sclerotic lesions, among the characteristics of multiple sclerosis, are not shown on brain MRIs but rather on scans of the spinal cord, where myelin sheath breakdown occurs.
While MS is thought to be an autoimmune illness, the exact reasons why some people are diagnosed with RRMS while others are afflicted with PPMS or another subtype remain unknown.
Because of the lack of a good animal model, PPMS research has been hampered for a long time. When studying multiple sclerosis, researchers frequently utilize mice with autoimmune encephalomyelitis. However, the condition is not reflected in the model due to the fact that PPMS appears to be spinal in origin.
Researchers in this study used a simple approach by collecting cerebrospinal fluid (CSF) from 42 MS patients. The CSF is the fluid that fills the space between the skull and the spinal column. Data were analyzed from 17 individuals with PPMS, 13 with RRMS, and 12 with SPMS. Following collection, the CSF was administered into the channel that houses the spinal cord in mice.
Mice treated with PPMS patients’ cerebrospinal fluid exhibited motor deficits, such as weaker grips and drooping tails. Tissue analysis revealed that, similar to people with MS, these mice displayed areas of myelin destruction, as well as high pro-inflammatory stimulation of central nervous system support cells.
However, mice that were given CSF from people suffering from relapsing forms of the illness did not exhibit motor symptoms or myelin impairment.