In autoimmune disorders, malfunctioning immune cells turn against the body.
These cells attack the protective sheaths that surround neurons in the brain, which can eventually lead to a host of symptoms and conditions like paralysis, and in some cases be fatal.
Now, imagine if these wayward cells could be influenced to control the disease, rather than fuel it.
Research presented today at a of the American Chemical Society (ACS) shows that it’s possible — and could be a game-changer — when it comes to treating autoimmune diseases like multiple sclerosis (MS) and type 1 diabetes.
Current methods imprecise
While current immunotherapies can yield positive results, they tend to deal in broad strokes.
This approach can affect and potentially compromise the entire immune system, rather than dealing with just the cells that are causing problems.
Christopher Jewell, PhD, associate professor in the bioengineering department at the University of Maryland, and lead researcher on the study released today, told Healthline that his team set out to develop a form of immunotherapy that specifically targeted the problematic cells, leaving the rest of the immune system alone.
“We are working on autoimmune disease, where the body’s immune system mistakenly recognizes and attacks its own cells or tissues,” Jewell wrote in an email. “In multiple sclerosis, myelin — the matrix that insulates neurons — gets attacked by malfunctioning immune cells entering the brain. Existing therapies have been beneficial for patients, but are broadly acting, often leaving patients immunocompromised. So the drawbacks are that the therapies are not specific enough. They also require lifelong treatment and don’t cure disease or permanently stop progression.”
When good cells go bad
With autoimmune diseases, an immune cell can falsely recognize a beneficial antigen as a foreign invader. It’s then brought to the lymph nodes, where an immune cell known as a T cell attacks it.
In the case of MS patients, T cells attack the myelin sheath — the protective shield that surrounds neurons in the brain.
Because of the role the lymph node plays in this process, researchers targeted this area.
“It’s in the lymph node that these myelin-specific cells decide how to respond to myelin once they leave the lymph node,” said Jewell. “Our idea was to inject degradable polymer particles directly into lymph nodes that slowly degrade in these tissues to release signals that tell the myelin-specific cells to become regulatory T cells that can control disease, instead of inflammatory T cells that drive disease.”
Jewell says these polymer particles are loaded with myelin fragments along with low doses of regulatory drugs in order to change the way the cells respond to myelin.
From there, these regulatory, beneficial T cells leave the lymph node and migrate to the brain to control the inflammatory T cells that are attacking the myelin sheath.
The particles are also just large enough to stop them from draining out of the lymph node, meaning the signals are able to not just influence existing cells but also the cells that are developing in the local tissue.
“We want to try to locally program the function of lymph nodes, but still achieve a selective and system-wide therapeutic effect,” said Jewell. “This is different from other particle-based approaches being tested that involve systemic administration, such as IV, that exposes the entire host to the immunosuppresants and regulatory signals.”
Other potential applications
The research team found success with their methods.
The particle injections were able to return the power of movement to paralyzed mice.
The next steps for the researchers include testing their methods on other mice, such as those who have had transplants or type 1 diabetes.
Later this year, they plan to collaborate with clinicians from the University of Maryland School of Medicine to perform tests on nonhuman primates.
This next round of testing will provide further insights, says Jewell.
“Mouse models of MS recreate some features of human disease, but they also lack some of the important characteristics,” he said. “So testing in a setting that is closer to humans is important to understand the benefits and limitations of our idea.”
If testing goes well, the plan is to eventually use this form of therapy for humans with autoimmune diseases like MS and type 1 diabetes.
“One of our goals is to use this unique platform to study lymph node function and how best to promote tolerance, so we’re excited about the new insight we are contributing using intra-lymph node delivery of particles as a tool,” wrote Jewell. “Of course, we also hope to contribute to better options for patients and we are currently working in pre-clinical models of both MS and diabetes.”
When asked where this technology could be 10 years from now, Jewell said that he hopes it not only leads to improved forms of immunotherapy but also a better understanding of how the lymph node functions.
“I hope that we’ve been able to use the unique control we have over the lymph node environment to give the field new information about how immune tolerance works,” he wrote. “The more knowledge we have in the field, the better chance we have for scientists and engineers to create more effective and selective treatments to stop autoimmune disease. We will also keep pushing forward on the therapeutic aspects to see if it might be translatable to humans.”