Summary:
Researchers are working on an innovative approach to treating a rare autoimmune disease of the peripheral nervous system, using a kind of molecular sponge made of sugar to remove pathogenic antibodies from the bloodstream. Developed to treat anti-MAG neuropathy, the approach also has potential applications in the treatment of other autoimmune diseases.
AMG neuropathy:
Patients with anti-MAG neuropathy suffer from loss of sensitivity in the arms and legs, neuropathic pain and loss of coordination that can impair mobility. With progressive damage to the peripheral nerves, patients are becoming increasingly restricted in their day-to-day lives until they require full-time care.
The disease is identified in the blood serum samples with autoantibodies that bind to the myelin-associated glycoprotein (MAG) in the peripheral nervous system. These anti- MAG antibodies have long been the cause of the disease. Reduction in the antibody concentration in the blood leads to improvement of the symptoms.
Until today there is no approved treatment that specifically targets these autoantibodies. Current treatment aims only to suppress the immune response they are inefficient and, in some cases, cause serious side effects.
The artificial molecule as a sponge.
Researchers are working on a new treatment with customized synthetic glycopolymers that work like a sponge on the harmful antibodies. The glycopolymer stimulates the section of the MAG protein to which the anti-MAG bind.
The scientists showed in vitro that the glycopolymer neutralizes the antibodies in the patient’s serum that cause the disease. The anti-MAG antibodies in immunized mice were also removed effectively.
Potential to treat other autoimmune diseases.
This new treatment method offers significant potential not only for antigen-specific treatment of anti-MAG neuropathy but also for other antibody-mediated autoimmune diseases.
As we have only fragmentary knowledge of the antigens in many autoimmune diseases, antigen-specific treatment methods are usually difficult to develop. The use of glycopolymers opens new possibilities in the treatment of diseases in which anti-glycan antibodies play a role. Examples of such diseases include multifocal motor neuropathy or Guillain-Barre syndrome.
Collaboration with spin-off
The findings arose from a joint project between the University of Basel’s Department of Pharmaceutical Sciences and Polyneuron Pharmaceuticals AG, a University of Basel spin-off founded by Dr. Ruben Herrendorff, Professor Andreas Steck and Professor Beat Ernst in 2014. The project was funded by the Commission for Technology and Innovation (CTI), the Gebert Rüf Foundation, and the Neuromuscular Research Association Basel.
Polyneuron Pharmaceuticals AG is currently preparing for the clinical trial of the glycopolymer drug for the treatment of anti-MAG neuropathy.