Microparticle therapy cures multiple sclerosis in mice, will it work in humans?

Currently, there is no permanent cure for MS, existing treatment options can only limit the symptoms or provide temporary relief.

However, in their latest study, the JHM claims that their mice experiment could pave the path for an effective MS treatment in humans.

The secret to reversing MS in mice

During their study, the researchers realized that the only way to reverse MS-like symptoms in mice was to reduce the effect of effector T cells that attack the myelin, by introducing more regulator T cells (T regs) that actually suppress the immune response.

In order to achieve this, they created biodegradable microparticles comprising three therapeutic components, each serving a different purpose:

• The first component was interleukin-2, a protein mixture that promoted the growth of Tregs. 

• The second component was MHC (major histocompatibility complex) class II, a molecule that provided extra protection to nerve cells by providing them with an additional myelin peptide covering.    

• Rapamycin, the third component negatively affected the effector T cell population by suppressing immune system activity. 

They injected the microparticles into the lymphatic system of the mouse models suffering from autoimmune encephalomyelitis, a medical condition in mice that result in symptoms similar to those found in MS patients. 

The therapy resulted “in the reversal of the MS-like symptoms in 100% of the mice, and even more exciting, achieving a full recovery in 38% — in other words, more than a third were cured of their disease,” said Georgio Raimondi, one of the study authors and an assistant professor at JHM.

The findings of the study demonstrate that in all of the mice, the T regs were able to overpower the damaging immune response of effector T cells against myelin. 

The therapy successfully prevented further nerve damage and gave the mice’s nervous system the time it needed to recover.

When can we expect an MS treatment for humans?

After seeing success in MS mouse models, the JHM team is excited to test their microparticles against other autoimmune disorders. They will soon check the effectiveness of their method on mice with type 1 diabetes.

“To engage and grow T regs specific for the insulin-producing cells in the pancreas damaged or threatened by that disease’s autoimmune activity, we’ll exchange the myelin peptide we used in the MHC-peptide portion of the MS therapy with one from those cells,” said Jamie Spangler, senior study author and an assistant professor at the John Hopkins Whiting School of Engineering. 

To make the treatment work for autoimmune disorders other than MS, all they need to do is replace the myelin peptide in the MHC molecule (one of the microparticle components) with another suitable peptide, but that doesn’t mean the microparticle injection is ready for human use.

It represents only an initial step in the process of treating MS symptoms. Before the procedure could be deemed completely safe for use in human trials, it had to first be tested on many animal models. 

The study is published in the journal Science Advances.

Study Abstract:

Multiple sclerosis (MS) is an autoimmune disease characterized by autoreactive immune cells damaging myelinated nerves, impairing brain function. Treatments aim for tolerance induction to reeducate the immune system to recognize myelin as “self” rather than “foreign.” As peripheral immune tolerance is primarily mediated by regulatory T cells (Tregs), we developed a therapy to support Treg expansion and activity in vivo. To target, engage, and activate myelin-specific Tregs, we designed a biodegradable microparticle (MP) loaded with rapamycin and functionalized with a biased interleukin-2 (IL-2) fusion protein and a major histocompatibility complex (MHC) class II loaded with a myelin peptide. These tolerogenic MPs (Tol-MPs) were validated in vitro and then evaluated in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Tol-MPs promoted sustained disease reversal in 100% of mice and full recovery in 38% of mice with symptomatic EAE. Tol-MPs are a promising platform for the treatment of autoimmune diseases.