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Microparticles may reverse MS symptoms in mice
June 07, 2023
Findings from a new study provide strong support for the ability to reverse — and in many cases, completely alleviate — MS-like symptoms in mice. There currently is no cure for MS. Although rarely fatal, MS can lead to long-term disabilities, and impair movement, muscle control, vision and cognition.
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 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.
Researchers at Johns Hopkins Medicine 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. Using this therapy on mice bred to exhibit symptoms modeling those seen in humans with MS, they found they could enhance the growth of T regs while simultaneously reducing the number of effectors, resulting in reversal of the MS-like symptoms in 100 percent of the mice, and even achieving a full recovery in 38 percent.
The researchers achieved these results by using biodegradable polymeric microparticles — tiny bioengineered polymer spheres — to deliver three key therapeutic agents: 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 to optimize the ones relevant to T reg expansion; a major histocompatibility complex 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; and rapamycin, an immunosuppressant drug that helps lower the number of effector T cells.
They injected 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. The researchers said their findings showed that in all of their 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, the MS-like mouse disease was completely cured in more than a third of the animals.
Results of animal model studies sometimes do not translate to humans and may be years away from being a marketable treatment. Researchers admit further studies will be required to confirm the effectiveness of their potential MS therapy.
The study appears in the journal
Science Advances
.
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