Destroying Myelin-damaging Immune Cells May Be New Therapy

Vesicles containing the chemotherapeutic agent doxorubicin can be used to destroy the aberrant, myelin-damaging immune cells that contribute to multiple sclerosis (MS), suppressing the progression of the neurodegenerative disorder, according to recent research findings using a mouse model.

If further validated, this technique could provide physicians with a new way to treat MS.

“We strongly believe that our therapeutic strategy … will become a new therapy for MS and make a new avenue of hope for MS patients,” the researchers wrote.

The study detailing these results, “New strategy for MS treatment with autoantigen-modified liposomes and their therapeutic effect,” was published in the Journal of Controlled Release.

MS is an autoimmune disorder in which cells of the immune system mistakenly attack a substance called myelin, which insulates nerves to protect them and accelerates the transmission of electrical signals. The loss of myelin results in nerve signal decay, leading to many of the symptoms associated with MS.

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Current treatments ease MS symptoms but cannot target the disorder’s underlying cause, which still is not completely understood. Scientists do not know, for instance, exactly what myelin component invites attack by immune system cells, such as T-cells.

Regardless of why they do it, knowing that immune system cells such as T-cells target myelin could advance the development of more effective therapies. With that in mind, a team of researchers from several Japanese institutions designed an experimental therapy that targets and destroys those immune cells, thereby preventing them from attacking and damaging myelin.

Their strategy consisted of putting doxorubicin, a cell-killing, or cytotoxic, drug inside of a sphere of fatty molecules called a liposome, whose outer surface they coated with myelin components. The hope was that autoimmune cells would recognize the liposomes and latch onto them as they would latch onto myelin. This would allow the liposome to bond with the cell and dump its therapeutic payload into it.

The team tested this strategy in mice with experimental autoimmune encephalomyelitis (EAE) induced by a myelin component called myelin oligodendrocyte glycoprotein (MOG) — this is a common mouse model of primary progressive MS.

The investigators discovered that their therapy, designated MOG-LipDOX, suppressed EAE symptoms through targeting T-cells, a class of immune cells primed to attack “foreign” molecules that invade the body, such as viruses and bacteria.

Specifically, the treatment successfully suppressed symptoms for more than 100 days and completely cured two mice — and without weight changes or signs of liver damage.

Importantly, the researchers found no evidence of immune cells infiltrating the central nervous system or CNS, which consists of the brain and spinal cord and is where the loss of myelin takes place.

“These results,” the team wrote, “suggest that treatment with MOG-LipDOX could prevent the demyelination of neurons caused by immune-cell invasion.”

Various subsets of T-cells exist, each carrying out slightly different functions. In MS, subsets of T-cells known as effector Th17 cells, and regulatory T-cells called Tregs, are strongly involved in MS progression, with the first causing nerve damage and the second protecting from it.

Here, the researchers examined T-cell populations and found that MOG-LipDOX’s main effect on these cells was to suppress effector Th17 cells while boosting the production of Treg cells. This, they suggested, may regulate the onset of MS.

Finally, the team observed the same effects in EAE mice induced with a myelin proteolipid protein (PLP) peptide — a model for relapsing-remitting MS. In this model, the liposomes were instead directed against cells recognizing the PLP protein and were called PLP-LipDOX.

Most MS patients show relapsing-remitting symptoms and overcoming this type of MS, the scientists wrote, “promises to have the strongest impact as a treatment goal of MS.”

“The present study suggests that the use of these autoantigen-modified liposomes promises to be a suitable therapeutic approach for the cure of MS,” they concluded.