Microparticle Therapy Offers a Glimmer of Cure for Multiple Sclerosis

Approximately 3 million individuals worldwide, with nearly a third residing in the United States, are affected by multiple sclerosis (MS) as per the federal government’s National Institute of Neurological Disorders and Stroke. MS is an incapacitating neurological disease characterized by the immune system's erroneous attack on nerves transmitting information to the central nervous system (comprising the brain and spinal cord). Despite its non-fatal nature, MS can result in enduring disabilities, impeding movement, muscle control, vision, and cognition, with no existing cure.

However, a breakthrough study by Johns Hopkins Medicine proposes that delivering therapy through microparticles could be a groundbreaking approach to halting multiple sclerosis (MS) and other autoimmune diseases, offering hope for reversing and alleviating MS-like symptoms in mice (1^✔ ✔Trusted Source
Bioengineered particles expand myelin-specific regulatory T cells and reverse autoreactivity in a mouse model of multiple sclerosis

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The study appears today in the journal Science Advances.

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Revolutionary Promise of Microparticle Therapy

For an unknown reason in people with MS, some of the body’s first line of defense against foreign invaders - immune cells known as CD4+ T cells - fail to recognize that myelin (the fatty material surrounding and protecting nerve cells) is a normal part of the human system.

If these wayward, or effector T cells, become dominant, they may provoke inflammation that damages or destroys the myelin sheath, which in turn, can severely disrupt or curtail transmission of nerve impulses from all parts of the body to the brain.

“We developed a method for ‘tipping the balance’ of the T cells reaching the central nervous system from effectors to regulatory T cells, or T regs, that modulate the immune system and have been shown to prevent autoimmune reactions,” says study co-senior author Giorgio Raimondi, Ph.D., M.Sc., associate director of the Vascularized Composite Allotransplantation Research Laboratory and assistant professor of plastic and reconstructive surgery at the Johns Hopkins University School of Medicine.

“Using this therapy on mice bred to exhibit symptoms modeling those seen in humans with MS, we found we could enhance the growth of T regs while simultaneously reducing the number of effectors, resulting in 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.”

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Breakthrough Study Reverses MS-like Symptoms

The researchers achieved these intriguing results by using biodegradable polymeric microparticles - tiny bioengineered polymer spheres - to deliver three key therapeutic agents:

1. A fusion of two proteins: Interleukin-2 (IL-2), which stimulates T cell production and growth, and an antibody that blocks certain binding sites on IL-2 to optimize the ones relevant to T reg expansion.
2. A major histocompatibility complex (MHC) class II molecule: With a myelin peptide (protein fragment) “presented” on its surface to immunologically select myelin-specific (and therefore, protective of the nerve cell covering) T regs rather than other T cell types.
3. Rapamycin, an immunosuppressant drug: That helps lower the number of effector T cells.

“We inject the loaded microparticles near lymphatic tissues to stimulate the production and growth of T regs and facilitate their travel to the central nervous system via the lymphatic system,” says study co-senior and corresponding author Jordan Green, Ph.D., director of the Biomaterials and Drug Delivery Laboratory and professor of biomedical engineering at the Johns Hopkins University School of Medicine.

“Our study findings showed that in all of our mice, the T regs stopped the autoimmune activity of the effectors against myelin, prevented further damage to the nerves, and gave them the time needed to recover.”

Furthermore, Raimondi says, the MS-like mouse disease, experimental autoimmune encephalomyelitis, was completely cured in more than a third (38%) of the animals.

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Promising Approach to Tackling Autoimmunity

Along with further studies to confirm the effectiveness of their potential MS therapy, Raimondi, Green, and their colleagues plan to try their microparticle therapy-delivery system on other autoimmune diseases.

"First in line will be a mouse version of type 1 diabetes,” says study co-senior author Jamie Spangler, Ph.D., director of the Spangler Lab at the Johns Hopkins University School of Medicine, and assistant professor of biomedical engineering and Chemical and biomolecular engineering at The Johns Hopkins University Whiting School of Engineering. “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.”

“Thebelief is that by simply changing the presented peptide each time, we can target our therapy to tackle a wide variety of autoimmune diseases,” adds Green. “We hope to have a cache of potential therapies ready to go before moving forward to safety and efficacy studies in mice, followed hopefully by human trials."

Reference:

1. Bioengineered particles expand myelin-specific regulatory T cells and reverse autoreactivity in a mouse model of multiple sclerosis - (https://www.science.org/doi/10.1126/sciadv.add8693)

Source-Eurekalert