New Immunotherapy for Neuropathy

It begins with tingling, followed by numbness in the fingers and feet, and later progresses to tremors and balance issues that make walking unsteady and increasingly difficult. Over the years, the condition advances, progressively restricting those affected. A patient at the specialized neuroimmunology clinic at Jena University Hospital had reached a point where she could only walk short distances, supported on both sides, while climbing stairs was nearly impossible. Yet, even after the cause of her symptoms was finally identified—an autoimmune-mediated disorder of the peripheral nervous system—efforts to stabilize the condition proved unsuccessful.

No Curative Treatment Therapie for Autoimmune Nerve Disease 

This is because there is currently no approved treatment that targets the cause of the disease. Triggered by a malfunction, the immune system produces massive amounts of IgM antibodies in this disease, that attack the myelin sheaths enveloping the nerves. Consequently, these sheaths can no longer perform their vital functions—supporting signal transmission and protecting and nourishing the nerve fibers.  This impairs nerve impulse conduction, and over time, nerve cells die off. Corticosteroids or other agents that suppress the immune response are used to improve the condition, while plasmapheresis can reduce the level of pathogenic antibodies in the blood. However, in this patient, these measures yielded only minimal and short-lived benefits. A second patient at the specialized clinic, who had an even longer history of the disease, experienced the same outcome. 

New Treatment Approach 

Dr. Jonathan Wickel and Dr. Mihai Ceanga, the patients' attending physicians, therefore sought a new treatment approach. To this end, they utilized the active agent teclistamab, a drug normally used to treat multiple myeloma. In this form of bone marrow cancer, plasma cells—a type of white blood cell—proliferate uncontrollably, thereby impairing healthy blood cell formation and bone metabolism. The drug directs T-cells, the body's own immune cells, straight to the abnormal plasma cells so that they can destroy them. The neurologists sought to leverage precisely this mechanism, as the pathogenic antibodies driving the nerve disorder are produced by these plasma cells. 

Rapid and Marked Improvement 

In a compassionate use setting, the two patients received four injections of the medication over a period of six weeks. Both patients showed a surprisingly rapid and significant improvement. Within a few weeks, the patients were able to walk considerably more confidently and over longer distances. Monthly clinical and laboratory examinations documented this improvement: “The causative IgM antibodies and paraproteins were no longer detectable in the blood after only a short time. We also found fewer neurofilaments, which enter the bloodstream as fragments during the breakdown of nerve cells,” said Jonathan Wickel. Ultrasonic scans showed a reduction in inflammatory processes affecting the nerves, and nerve function improved significantly. Mihai Ceanga: “Some nerves that had shown no measurable response at all during pre-treatment electroneurography became electrically detectable again. Overall, nerve conduction recovered significantly.” Also of importance: Neither patient has experienced any severe side effects since the treatment more than a year ago.
“These two cases proof that modern cancer immunotherapies may also be effective in treating autoimmune diseases. In this instance, we were able to specifically target the antibody-producing cells rather than merely treating the consequences of the autoimmune reaction. Clinical trials are now required to substantiate the safety and efficacy of this treatment approach," Prof. Dr. Christian Geis, Director of the Department of Neurology at Jena University Hospital, in his assessment of the findings. The scientists reported their findings in Nature Communications.