Primary progressive multiple sclerosis (PPMS) is the fastest-progressing version of multiple sclerosis (MS), generally characterized by a steady decline in neurological function. Unlike relapsing-remitting MS (RRMS), which is the more common form of the disease, patients with PPMS do not display distinct relapses or remission periods. PPMS can cause severe disability within just a few years of symptom onset. Fortunately, recent research into a sponge-like protective mechanism within the central nervous system of mice could offer hope for multiple sclerosis treatment. Read on for a summary of the research, which was published in February in the journal Proceedings of the National Academy of Sciences.
Hurdles in Multiple Sclerosis Treatment
In MS, immune cells are known to attack the myelin sheath around nerves. This sheath is a protective, fatty layer that wraps around nerve fibers, providing insulation. Once the sheath is compromised, the underlying nerves become damaged. However, researchers don’t yet understand how immune cells impact the myelin sheath. To understand the mechanism of the attack, researchers must perform biopsies of the brain and spinal cord, which is not possible in living patients with active MS. This stands in the way of effective treatment development. Currently, there is no FDA-approved drug offering full remission for patients with MS.
To better observe the mechanism that damages the myelin sheath, the researcher behind the aforementioned study used a unique, sponge-like implant also known as a scaffold. The implant has been used to study MS previously — specifically, to diagnose relapsing MS. This time, the implant was used to create an easily biopsied “cell sponge” in mice that were treated with myelin-oligodendrocyte-glycoprotein (MOG) to induce the MS-like autoimmune condition chronic progressive experimental autoimmune encephalomyelitis (EAE).
Working with MS Mouse Models
The sponge-like scaffold used in the research is a shockingly small cylinder of biodegradable polyester, just 13 millimeters in diameter and 2 millimeters in height. The scaffold is full of small pores, allowing cells to attach — similar to the way a sponge absorbs liquid. The research team implanted the scaffold just under the skin of mice. Then, the team induced progressive experimental EAE in half of the mice, while the other half served as a healthy control.
The immune cells in both mice were attracted to the scaffold, ultimately growing within the pores of the “sponge,” along with other cells. The team could then remove the scaffold and biopsy the tissue without compromising the sensitive central nervous systems of the mouse subjects.
A Surprising Multiple Sclerosis Treatment Target
To analyze the tissue, the research team honed in on single-cell RNA sequencing to discover the behavior of individual cells. In the progressive experimental EAE mice, the team observed that a group of proteins called CC chemokines were particularly overactive. These proteins help fight infection, but they can also trigger immune cells to attack healthy tissue, as in autoimmune conditions.
The team then focused on ways to disrupt overactive CC chemokines. They worked to develop tiny injectable nanoparticles specifically designed to surround a key CC chemokine and disrupt its overactivity, thereby preventing autoimmune symptoms from developing. The nanoparticle treatment also reduced symptoms in the mice by more than half when given after disease onset.
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While the research still has to be translated to human subjects, the insights into CC chemokines could prove valuable in developing multiple sclerosis treatment, with the ultimate goal of slowing or stopping degenerative MS. “The scaffold provides an unprecedented ability to track disease dynamics and to investigate the underlying mechanisms, particularly at early stages,” said Lonnie Shea, the Steven A. Goldstein Collegiate Professor of Biomedical Engineering and co-corresponding author of the study. “Therapies targeting these early mechanisms can halt disease progression before significant tissue damage.”
To study MS and test new compounds against this disease, Scantox Neuro offers research in the induced EAE and cuprizone mouse model. Different treatment regimens are available to induce typical MS symptoms and pathologies. EAE-induced mice can be evaluated for clinical signs, muscle weakness, neurofilament light chain levels as markers of neurodegeneration, and demyelination.
Scantox is the leading Nordic preclinical GLP-accredited contract research organization (CRO), delivering the highest grade of pharmacology and regulatory toxicology services since 1977. Scantox focuses on preclinical contract research services, supporting pharmaceutical and biotechnology companies with their drug development projects. Core competencies include explorative and efficacy studies, PK studies, general toxicology studies, local tolerance studies, wound healing studies, and vaccines. To learn more about our services and areas of study, please subscribe to our newsletter. And if you’re interested in partnering with us, please contact us online.
