MS Society-funded study explores ‘nanoparticles’ as a potential therapeutic strategy in mice with an MS-like disease
One of the challenges facing multiple sclerosis researchers is discovering new ways to stop the process whereby the immune system attacks its own body tissues – termed autoimmunity – while leaving the general immune system intact to fight infection. A key priority in research is to develop ways of specifically targeting the disease-causing immune cells; in this case, certain white blood cells that have “gone rogue” and seek out proteins expressed by the myelin sheath around nerve fibres, thus leaving myelin vulnerable to attack.
Research being conducted by Dr. Pere Santamaria and his team at the University of Calgary is exploring a new class of drugs that could offer a therapeutic strategy for MS and other autoimmune diseases by specifically targeting and “reprogramming” disease-causing white blood cells to blunt their harmful activity. This technique relies on using nanoparticles – tiny particles many times smaller than cells – which are being explored as a drug delivery system. After coating nanoparticles with a certain myelin-specific proteins, Dr. Santamaria posited that exposure of disease-causing white blood cells to these coated nanoparticles would take advantage of a naturally occurring immune process that would convert them into benevolent white blood cells.
In a paper published in the prestigious journal Nature, Dr. Santamaria and his team, including MS Society-funded investigator Dr. Wee Yong, explored the ability of nanoparticle therapy to reduce disease activity in mice with an MS-like disease. This study was supported by an operating grant from the MS Society of Canada.
Study Methods and Results
The authors studied the therapeutic potential of nanoparticles coated with disease-specific proteins in animal models of various autoimmune diseases, including type 1 diabetes, arthritis, and multiple sclerosis. Mice with an MS-like disease were treated with nanoparticles coated with myelin oligodendrocyte glycoprotein (MOG), a component of myelin that is a target for disease-causing white blood cells. The authors measured the effects of the coated nanoparticles on various measures of disease activity – including clinical disability, inflammation and demyelination in the central nervous system, activation of disease-driving microglia and macrophages – and compared these treatment effects with the effects of various mock solutions.
The authors found that MOG-coated nanoparticles blunted disease progression and improved clinical disability in mice with an MS-like disease compared to the mock solutions. Improvements in clinical function were accompanied by reductions in activated microglia and macrophages in the brain, and fewer areas of inflammation and demyelination in regions of the brain and spinal cord. They were also able to confirm that the overall number of non-disease-causing white blood cells was increased in mice that had been exposed to the nanoparticle therapy. The authors also characterized some of the mechanisms of action that are thought to underlie the process by which nanoparticle therapy “reprograms” disease-causing white blood cells.
The results of this study represent an exciting development in the saga for developing more specific therapies for MS. Nanoparticles join a growing number of experimental therapies that comprise the “next-wave” of targeted therapies that take a more nuanced approach to homing in on disease-causing immune cells rather than adopting the traditional “blunt-force” tactic of immunosuppression. An added benefit of this strategy is the ability to swap out the disease-specific proteins that coat the nanoparticles, opening up the pathway to treating a suite of autoimmune diseases, such as type 1 diabetes and arthritis.
In order to accelerate the translational potential of these findings, Dr. Santamaria and his team are developing the nanoparticle technology into a tractable drug therapy through his biotechnology company Parvus Therapeutics, Inc.
Clemente-Cesares, X et al. (2016) Expanding antigen-specific regulatory networks to treat autoimmunity. Nature. 530:434-40
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