In multiple sclerosis, a misdirected immune response damages the protective myelin sheaths surrounding the nerve fibers in the central nervous system.
Scientific Frontline: Extended "At a Glance" Summary: Targeted Erythrocyte-Coupled Therapy for Multiple Sclerosis
The Core Concept: A novel, targeted therapy for multiple sclerosis utilizes the body's own red blood cells to train the immune system to tolerate endogenous structures, preventing it from attacking the central nervous system.
Key Distinction/Mechanism: Unlike existing multiple sclerosis treatments that broadly suppress the entire immune system, this approach couples specific protein antigens to erythrocytes. As these aging red blood cells are naturally broken down in the liver and spleen, the attached antigens are presented to the immune system in a manner that promotes specific tolerance, thereby halting the autoimmune attack on myelin sheaths without systemic immunosuppression.
Major Frameworks/Components:
- T lymphocytes: The primary immune cells responsible for driving the autoimmune disease by mistakenly attacking the central nervous system.
- Erythrocytes: Autologous red blood cells acting as carriers for specific protein constituents to redirect the immune response.
- Antigen-specific tolerance: The immunological mechanism wherein the natural degradation of peptide-coupled red blood cells induces regulatory tolerance rather than an inflammatory attack.
- Myelin sheaths: The protective coverings surrounding nerve fibers in the brain and spinal cord, which are damaged by the misdirected immune response.
Branch of Science: Immunology, Neurology, Clinical Pathology, and Biotechnology.
Future Application: Pending further clinical trials coordinated by the spin-off biotech company Cellerys, this antigen-specific tolerance principle could potentially be adapted to treat over one hundred other identified autoimmune diseases.
Why It Matters: With autoimmune diseases affecting more than 5 percent of the global population, developing a targeted treatment that eliminates the widespread immunosuppressive side effects of current therapeutics represents a significant advancement in managing chronic inflammatory conditions.
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 to 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 nonspecific 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 clinical trial results for a novel MS therapy. 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 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 100 autoimmune diseases.” In general, autoimmune diseases have increased steadily over recent decades and affect more than 5% 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 it 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,” says last author Roland Martin from 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.
Funding: In the clinical trial, the new therapy was tested for the first time on 10 patients with multiple sclerosis. It was funded by Wyss Zurich.
Published in journal: Proceedings of the National Academy of Sciences
Authors: Andreas Lutterotti, Thomas Ludersdorfer, María José Docampo, Muriel Morax, Helen Hayward-Koennecke, Pietro Oldrati, Vasileia Kalaitzaki, Zoe Marti, Angela Zaugg, Mattias Bronge, Olivia G. Thomas, Filipa Marques Ferreira, Carla Sellés Moreno, Carolina Cruciani, Reza Naghavian, Jacobo Sarabia del Castillo, Laure Tillé, Markus Reindl, Pavlos C. Englezou, René Stenger, Ilijas Jelcic, Nikolai Pfender, Marc Hilty, Magdalena Foege, Federica Guffanti, Verena Weichselbaumer, Alain Blanc, Thorsten Buch, Martin Hüllner, Sebastian Winklhofer, Valerie Treyer, Jeroen S. Goede, Martin Behe, Massimo Broggini, Eugenio Scanziani, Tomas Olsson, Hans Grönlund, Maria Pia Sormani, Martin Kayser, Mireia Sospedra, and Roland Martin
Source/Credit: Universität Zürich
Edited by: Scientific Frontline
Reference Number: imgy090126_01
