A new study using microparticle therapy to boost the number of ‘good’ immune cells has reversed the nerve cell damage in mice with multiple sclerosis-like symptoms and cured more than a third. The finding has the potential to lead to new treatments for not only multiple sclerosis but other autoimmune diseases like type 1 diabetes.
Multiple sclerosis (MS) is an incurable autoimmune disease caused by the body’s immune cells mistakenly attacking the nerves that send information to the brain and spinal cord. The condition affects nearly 3 million people worldwide.
Effector T cells are part of the body’s first line against invaders. However, in MS, they fail to recognize that the protective fatty sheath (myelin) that covers nerve cells is a normal part of the body and attack it, causing inflammation and damage. Damage to the myelin interferes with the transmission of nerve impulses from all over the body to the brain. Regulatory T cells – T regs – on the other hand, are known to suppress excessive inflammation in autoimmune diseases.
In a new study, researchers from John Hopkins Medicine have used a treatment delivered via microparticles to mice with MS-like symptoms that shows promise as a treatment for this debilitating disease. Their rationale was simple: if they overpowered the ‘bad’, effector, T cells with ‘good’ ones, T regs, it might stop the effector cells from destroying the myelin sheath.
“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,” said Giorgio Raimondi, one of the study’s co-authors.
The researchers’ method involved injecting biodegradable polymeric microparticles into the lymphatic tissue of the mice to deliver three key therapeutic agents. The first was a fusion of two proteins, interleukin-2, which stimulates T cell production and growth, and an antibody that blocks certain binding sites on IL-2 but optimizes the ones relevant to T regs. The second was a molecule with a myelin protein fragment (peptide) "presented" on its surface that selects myelin-specific T regs that protect the nerve cell covering. And third, the drug rapamycin, an immunosuppressant that lowers effector T cell numbers.
The lymphatic system is part of the immune system, a large network of vessels, nodes, organs and tissues that keeps body fluid levels in check and defends against infections. The fluid it carries, called lymph, contains white blood cells.
“We inject the loaded microparticles near lymphatic tissue to stimulate the production and growth of T regs and facilitate their travel to the central nervous system via the lymphatic system,” said Jordan Green, corresponding author of the study. “Our study finding showed that in all of our mice, the T regs stopped the autoimmune activity of the effectors against myelin, prevented further damage to the nerve and gave them the time needed to recover.”
The findings impressed the researchers.
“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 order words, more than a third were cured of the disease,” Raimondi said.
The researchers plan to confirm the effectiveness of their novel microparticle treatment for MS with further studies, with a view to tackling type 1 diabetes, another autoimmune disease, in the near future.
“First in line will be a mouse version of type 1 diabetes,” said Jamie Spangler, a study co-author. “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 … with one from those cells.”
The researchers believe that their treatment has the potential to treat a number of autoimmune diseases.
“The belief is that by simply changing the presented peptide each time, we can target our therapy to tackle a wide variety of autoimmune diseases,” said 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.”
The study was published in the journal Science Advances.
Source: John Hopkins Medicine
