Friendly Fire: When Your Immune System Attacks

Creating a targeted therapy for autoimmune diseases

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When we begin to feel unwell, we may first suspect that a pathogen like bacteria or a virus is making us sick. But, would you believe that your own body is also capable of attacking itself, and could actually be the one responsible for making you sick? This is the case for as many as 23.5 million Americans who suffer from autoimmune diseases, according to the National Institutes of Health.

Autoimmune disease occurs when the body’s immune system mounts a response against native cells or tissues - essentially attacking itself. There are over 80 identified diseases unified by the common underlying cause, which is an overactive immune system. However, these diseases often manifest with markedly different symptoms, ranging from stiff joints in rheumatoid arthritis to hypoglycemia in Type 1 diabetes.

Effective treatment options for autoimmune disease have been lacking. Patients typically are prescribed a regimen of immunosuppressant medication. The medication works broadly to dampen the overall activity of the immune system. While this alleviates the associated symptoms of autoimmune disease, it also leaves the body more susceptible to infection, and possibly even the development of cancer.

However, researchers are making progress towards developing targeted therapies that will only turn off the malfunctioning components of the immune system. Such an approach would treat the autoimmune disease while preserving the immune system’s strength to fight off routine infections. The first step toward developing these new therapies has been to understand how the immune system normally functions and which steps go awry in autoimmune disease.

A healthy immune system has a similar defense mechanism to a castle. Like the high walls and fortified gate, our body also has a tough physical barrier to penetrate: the skin. When this barrier is breached by invaders (pathogens), soldiers on patrol rush on scene to slow down the invasion and signal for reinforcements. Our bodies’ soldiers are the immune system’s macrophages and dendritic cells, which circulate the body and filter any debris. The debris can consist of old or dead cells, and also proteins that have shed off nearby living cells. As they filter debris, macrophages and dendritic cells analyze for the presence of common pathogenic markers. If detected, they then recruit the help of B cells and T cells, highly specialized cells for destroying invaders.

Several factors, including family history and environmental exposure, are believed to affect the development of autoimmune disease. One possible source of environmental exposure may be an infection. Certain pathogens that cause infection possess markers very similar to those found on human cells. When invaded by these pathogens, the immune system learns to recognize these markers as dangerous. While this allows for successful elimination of the pathogen, what ensues could be described as a mad witch-hunt. The immune system, now highly suspicious of any cell carrying markers resembling the pathogen, puts all human cells on trial, and the cells displaying markers resembling those detected from the pathogens are sentenced to death. This large-scale destruction of beneficial human cells leads to autoimmune disease.

A promising therapy targeting the process of recruiting reinforcements is under development by Dr. Stephen Miller at Northwestern University’s Feinberg School of Medicine. In this therapy, macrophages and dendritic cells are removed from the body and manipulated to recognize the markers once again as native. This therapy is almost like a reverse vaccination.

Dr. Miller has developed his approach toward treating multiple sclerosis, and it was recently introduced into human clinical trials. In 2013, a report was published stating that Phase 1 of the clinical trials showed promising signs of patient safety and therapeutic efficacy.

However, one potential limitation to this treatment, which could hinder its widespread use, is the necessity of removing and then returning cells to the patient. This process is time intensive, complicated, and subsequently, very expensive. To address this issue, Dr. Lonnie Shea of Northwestern University’s McCormick School of Engineering has been working together with Dr. Miller to replace the cellular component of the therapy with nanotechnology.

Rather than take cells from the patient, in this new approach, tiny synthetic particles called nanoparticles would be used in place of the human cells. These nanoparticles are made from biocompatible materials that break down over time and are re-absorbed by the body. The nanoparticles would be fabricated with the markers and then delivered into the bloodstream. Once there, macrophages and dendritic cells would take up the nanoparticles, and thus be manipulated to identify the markers once again as native, and call off the reinforcements. The envisioned goal is to manufacture and administer the nanoparticles to patients as with traditional pharmaceutical drugs.

Preliminary studies of the nanoparticle therapy in disease models have shown great promise, and the therapy may soon advance to human clinical trials. If successful, this therapeutic approach would provide a significant advancement in available treatment options for multiple sclerosis. Moreover, this approach could be applied toward treating other autoimmune diseases, as well as allergies or even organ transplant tolerance. The main caveat, though, with targeted therapies for autoimmune disease, is that the markers identified by the overactive immune system must be known in order to be manufactured on the nanoparticles. Unfortunately, there is often not enough known about these diseases to identify the markers, which has slowed the progress for developing these improved therapies. 

As advancements in the fields of pathology and immunology increase our understanding of the precise markers characteristic to each autoimmune disease, the nanoparticle treatment approach may find new applications. Having a targeted treatment for these diseases would help to reduce the large incidence of autoimmune disease in America and around the world.

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