Targeted MS treatment protects the overall immune system

UZH researchers have developed a novel therapy for multiple sclerosis that is designed to stop the misguided immune response without suppressing the immune system as a whole. An initial clinical trial shows that the approach is safe and well tolerated. In addition, the demonstrated mechanisms of action are highly promising. The principle could also be applied for treating other autoimmune diseases.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that particularly affects young adults. The disease is driven by immune cells - primarily what are known as T lymphocytes. These cells normally fight off pathogens such as viruses, bacteria and fungi, as well as tumors, but in MS they mistakenly attack the brain and spinal cord. This can lead to a range of symptoms, including impaired vision, loss of sensation, paralysis and severe fatigue. Although effective treatments for MS already exist, all approved therapies suppress the immune system in a non-specific way and can sometimes cause significant side effects.

Immune system learns tolerance

A team of researchers from the University of Zurich (UZH), the Karolinska Institute in Stockholm, and several other collaborating institutions has now published the first results for a novel therapy for MS in a clinical trial. The new approach uses the body's own red blood cells (erythrocytes), to which specific protein constituents are attached. The misguided immune response in MS is then redirected toward these cells. After being returned to the body, these erythrocytes are absorbed and broken down like aging red blood cells, primarily in the liver and spleen. In the process, the attached antigens are presented to the immune system in a way that promotes tolerance. The intention is to train the immune system to stop attacking these endogenous structures.

This means that the misguided immune response in MS could be stopped in a targeted way without suppressing the immune system as a whole.

"This would make it possible to suppress this autoimmune disease in a very targeted manner and without major side effects," says lead author Andreas Lutterotti who had led the study at the Department of Neurology at the University of Zurich and the University Hospital of Zurich. "This approach can also be applied to many of the more than one hundred autoimmune diseases." In general, autoimmune diseases have increased steadily over recent decades and affect more than five percent of the population.

First step into the clinic

The clinical trial involving the first patients confirms that this new MS therapy shows good tolerability and safety and reveals promising mechanisms of action.

After more than two decades of development work, we've now cleared the first clinical hurdle to enable us to deliver the therapy to patients."

Roland Martin, last author, UZH's Institute of Experimental Immunology

However, the rest of the clinical development work is very costly and can no longer be conducted solely in an academic environment. This is why the researchers have set up the biotech company Cellerys. A forthcoming trial will investigate the clinical efficacy of the therapy once the required funding has been secured.