German researchers today unveiled the results of a study on a new procedure that safely resets a multiple sclerosis (MS) patient's immune system. It can reduce the body's attacks on the protective myelin sheath that insulates nerve cells in the brain.
For this small Phase 1 trial, which was a collaboration between Northwestern University’s Feinberg School of Medicine, University Hospital Zurich in Switzerland, and University Medical Center Hamburg-Eppendorf in Germany, ten patients were selected. Eight patients with relapsing-remitting MS (RRMS) and two with secondary progressive MS (SPMS) were enrolled initially, but one RRMS patient withdrew before the procedure.
Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin covering that insulates nerve cells in the central nervous system, which includes the brain and spinal cord. MS is a chronic, degenerative, and often disabling disease affecting more than 400,000 people in the U.S. and more than 1.2 million people worldwide. Symptoms can range from mild numbness to paralysis and blindness.
Pressing the Immune System's "Reset" Button
The study involved giving patients a single infusion of their own white blood cells, or T-cells, which were processed and then reintroduced into the body. The T-cells were used to deliver billions of myelin antigens into the bloodstream, forcing the patients' immune systems to recognize the antigens as harmless and build up a tolerance to them. An antigen is a substance that the body believes is a harmful invader. When the body detects an antigen, it releases antibodies to find and destroy it.
In patients with MS, the body creates antibodies to fight very specific antigens, in this case myelin-specific peptides, residing in the central nervous system. The seven antigens researchers used in this study were all proteins found in myelin. Using more than one antigen increased the odds that the correct antigen targeted by the patient’s immune system would be included.
The patients' T-cells were isolated and then coupled with all seven antigens used in the trial. The coupling was achieved using a chemical cross-linker called EDC that allows the antigens to stick to the T-cells but does not, itself, become part of that bond.
These T-cells, with their antigen hitchhikers, were then rinsed twice to remove the cross-linker and re-suspended in the patient’s blood plasma. This cocktail of antigen-spiked T-cells, suspended in plasma, was then given to the patient through an IV. The process from start to finish took about nine hours.
Seeing Dramatic Results
The results showed that the therapy was safe and reduced the patients’ immune system attacks on myelin by as much as 50 to 75 percent.
"The therapy stops autoimmune responses that are already activated and prevents the activation of new autoimmune cells," said Dr. Stephen D. Miller, Ph.D., a professor of microbiology and immunology at the Feinberg School of Medicine in Chicago, Ill., in an interview with Healthline. "Our approach leaves the function of the normal immune system intact. That's the holy grail."
According to the study, the side effects of the treatment were virtually non-existent. The only effect of note was one patient’s complaint about a “metallic taste” after the injection.
"This treatment should not lead to any major side effects (that is our hope and expectation) and be highly specific, i.e. leave normal immune responses that we need to defend ourselves against infections untouched," the study's principal investigator Dr. Roland Martin told Healthline.
What This Could Mean for MS Patients
For the hundreds of thousands of M.S. sufferers in the United States, this is perhaps the most promising news of a non-drug treatment to surface in years. Although there has been much recent excitement over FDA approval of several new drug therapies for MS, they are all part of either a daily, every-other-day, weekly, or monthly regimen to which a patient is indefinitely tied, at a cost that many cannot afford.
For safety reasons, this trial was conducted in a hospital setting, but if approved, the treatment will most likely be an outpatient procedure.
A single-dose treatment with no side effects, performed in an outpatient setting, that leaves a patient’s immune system intact sounds almost too good to be true. However, further testing is necessary to validate the safety and effectiveness of the procedure. “At this point we are trying to acquire funding to carry this process into a phase 2a trial,” Miller said.
When asked how long it might take to complete additional trials and the FDA approval process, Miller speculates, “Realistically, this could take three to four years.” Compared to other trials for new drugs and treatments, however, three to four years is practically the blink of an eye.
"The phase 2a trial is fully planned, and we have approached various funding sources, among them the European Union," Martin said. "We have also begun to discuss the project with pharmaceutical and biotech companies and hope to find support in the near future. The phase 2a trial will most likely be a two to four center study, and if a US center is interested, we are very open as long as this would not create a major extra hurdle with respect to regulatory filings."
Other Uses for The Procedure
“By switching the antigens attached to the patient's white blood cells, the therapy could be used to treat any autoimmune disease in which the targeted antigens are known,” Miller said. This means the technique could be used to sensitize the body to insulin in the case of type 1 diabetes, gliadin proteins in the case of Celiac disease, and joint proteins in the case of rheumatoid arthritis.
Although this procedure probably won't have a price tag for several years, Miller speculates that doctors could keep costs down by using nanoparticles as a delivery method for the antigens. Nanoparticles are tiny organic particles that target the immune system and are biodegradable, making them ideal for delivering substances like the antigens used in this study directly to the immune system.
“The use of nanoparticles would avoid the intrusive, complex, rather lengthy and costly process of collecting, purifying, and modifying the patient's white blood cells,” said Miller. “The particles are biodegradable and can be manufactured easily to FDA standards and would provide an 'off-the-shelf' material to which various antigens could be easily and efficiently attached.”
While further research is needed, this news is sure to be well received in the MS community, especially by those with SPMS, as little research has been done to address this or other progressive forms of the disease. Because of the adaptability of the process, patients suffering from other autoimmune diseases, facing an organ transplant, or fighting allergies may find the research promising as well.