A new way to treat multiple sclerosis by re-establishing immune tolerance

A new way to treat multiple sclerosis by re-establishing immune tolerance

Multiple sclerosis (MS) is a disease that affects the nervous system, causing inflammation and damage to the protective layer of nerve fibers. This leads to symptoms such as vision problems, fatigue, numbness, and difficulty walking. MS can be divided into two types: one that has episodes of inflammation followed by recovery, and one that has continuous worsening of disability without clear episodes.

There is no cure for MS, but there are treatments that can reduce the inflammation, slow down the disability, and improve the quality of life of patients. However, these treatments do not work for everyone, and they can also weaken the immune system and increase the risk of infections. Therefore, there is a need for better ways to treat MS that can target the specific cause of the disease without affecting the whole immune system.

A team of researchers from Canada and Korea have developed a new method that uses a biomaterial-based vaccine to treat MS by re-establishing immune tolerance. Immune tolerance is the ability of the immune system to recognize and tolerate the body’s own tissues and not attack them as foreign invaders. In MS, this tolerance is lost, and the immune system attacks the nerve fibers as if they were harmful.

The vaccine consists of tiny particles made of porous silica that carry a self-antigen and an inorganic nanoparticle. A self-antigen is a molecule that is normally present in the body and that triggers an immune response in MS. An inorganic nanoparticle is a metal oxide that can scavenge reactive oxygen species (ROS), which are molecules that cause oxidative stress and inflammation.

The researchers tested their vaccine in mice with experimental autoimmune encephalomyelitis (EAE), which is a model of MS. They injected the vaccine into the mice and observed its effects on their immune system and disease progression.

They found that the vaccine induced regulatory T cells (Tregs) in the spleen of the mice. Tregs are a type of immune cell that can suppress other immune cells and prevent them from attacking self-tissues. The vaccine also reduced the number of antigen-presenting cells (APCs) and autoreactive T cells in the central nervous system of the mice. APCs are immune cells that present antigens to T cells and activate them. Autoreactive T cells are T cells that recognize self-antigens as foreign and attack them.

The vaccine also enhanced antigen-specific immune tolerance in the mice. This means that the immune system became more tolerant to the specific self-antigen used in the vaccine, but not to other antigens. This is important because it means that the vaccine does not affect the overall immunity of the mice, but only targets the cause of MS.

The researchers also found that adding cerium oxide nanoparticles (CeNP) to the vaccine improved its effectiveness. CeNP are nanoparticles that can scavenge ROS and reduce oxidative stress and inflammation. They found that CeNP reduced the activation of APCs and enhanced antigen-specific immune tolerance more than silica nanoparticles alone.

The vaccine was able to reverse paralysis in mice with chronic EAE, which is similar to chronic MS in humans. The mice showed improvement in their motor function and nerve fiber integrity after receiving the vaccine.

The study, published in Nature Communications on December 2nd, 2022 1, is the first to use a biomaterial-based vaccine with self-antigen and inorganic nanoparticles to treat MS by re-establishing immune tolerance. The authors acknowledge some limitations of their method, such as the need for validation in human trials, the dependence on data availability and quality, and the potential ethical and regulatory implications of using self-antigens. However, they also highlight the potential benefits of their approach for personalized medicine and precision neurology in MS and other autoimmune diseases.

1: Nguyen TL et al., Immunosuppressive biomaterial-based therapeutic vaccine to treat multiple sclerosis via re-establishing immune tolerance. Nat Commun 13:7449 (2022). https://doi.org/10.1038/s41467-022-35263-9