A new treatment for multiple sclerosis (MS) that resets the patient’s immune system was found to be safe and well tolerated in a small trial published in Science Translational Medicine this week. And, although not designed to test the effectiveness of the therapy, the trial also showed promising results in this area.
Another important result is that the therapy does not appear to affect the immune system’s ability to defend against infection.
Current therapies for MS suppress the entire immune system, leaving patients more vulnerable to everyday infections and higher rates of cancer.
The results of the phase 1 trial showed the therapy was safe and well tolerated and also reduced immune system reactivity to myelin by 50 to 75%, say the researchers.
“The therapy stops autoimmune responses that are already activated and prevents the activation of new autoimmune cells,” says co-senior author Stephen Miller in a statement.
Miller is the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine in Chicago in the US.
MS is an autoimmune disease, a condition where the body’s immune system attacks and destroys healthy tissue. In the case of MS, the healthy tissue is myelin, the protein that insulates the nerves in the spinal cord, brain and optic nerve and stops the electrical signals from leaking out.
As the myelin is gradually destroyed, patients experience symptoms ranging from mild numbness in the limbs to paralysis or blindness.
In this study, the researchers used patients’ own white blood cells to reset their immune system so it stops attacking and destroying myelin.
For the study Miller collaborated with researchers at University Hospital Zurich in Switzerland and University Medical Center Hamburg-Eppendorf in Germany, where the nine patients who took part in the trial were treated.
The researchers filtered the white blood cells out of the patients’ blood, processed them and combined them with myelin antigens (the parts of the myelin protein that the immune system reacts to).
They then injected billions of the processed white blood cells, packed with myelin antigens, back into the patients.
The cells entered the spleen, which filters the blood and helps the body eliminate old and dying blood cells. It is during this process that immune cells recognize the myelin antigen as harmless. This was confirmed in the patients by immune assays, say the researchers.
Although nine patients are not enough to give a statistically meaningful result on how well the treatment halted progression of MS, the patients who received the highests dose of white blood cells showed the greatest reduction in reactivity to myelin.
The main goal of the study was to show the treatment was safe and well tolerated. It showed that injecting up to 3 billion white blood cells carrying myelin antigens resulted in no adverse effects in patients with MS.
The trial also showed that the new MS treatment did not reactivate the patients’ disease and it did not affect the ability of their immune system to react to real pathogens.
The researchers tested this last part by checking the patients’ response to tetanus. They had all received tetanus shots in their lifetime, and one month after receiving the MS treatment, their immunity to tetanus remained strong, suggesting the treatment had only affected their immune system’s reaction to myelin.
“Our approach leaves the function of the normal immune system intact. That’s the holy grail,” says Miller, whose lab has been working for more than three decades to reach the human trial stage.
With further testing the researchers believe the approach could be used to treat other autoimmune diseases and even allergies. You simply attach the appropriate set of antigens to the white blood cells.
Miller’s lab has already published some papers showing the therapy could be effective in treating type 1 diabetes and airway allergy (asthma). In a study published in the Journal of Immunology, they describe how they used the method to neutralize peanut allergy in mice, using white blood cells carrying peanut proteins.
Using a patient’s white blood cells is an expensive and labour-intensive way to deliver this therapy. Another recently published study where Miller and colleagues showed that nanoparticles can stop MS in mice, suggests nanoparticles may offer a cheaper and more accessible delivery vehicle than white blood cells. Cour Pharmaceutical Development Company now has the licence for the nanoparticle technology, which is undergoing preclinical development.
Researchers are now trying to raise $1.5 million to do a phase 2 trial, to see if the new treatment can halt the progression of MS in humans. The trial has already been approved in Switzerland.
“In the phase 2 trial we want to treat patients as early as possible in the disease before they have paralysis due to myelin damage,” says Miller, “Once the myelin is destroyed, it’s hard to repair that.”
Funds from the German Federal Ministry for Education and Research and the Cumming Foundation helped pay for the trial.
Another recently published study describes how researchers in Australia found an immune suppressor protein that may offer a way to reverse type 1 diabetes and suggests if it works for that disease then it may well work for other autoimmune diseases like MS.
Written by Catharine Paddock PhD