| Title: |
Development of therapeutic glycopolymers for the treatment of peripheral neuropathies and viral infections |
| Authors: |
Aliu, Butrint |
| Contributors: |
Ricklin, Daniel; Ernst, Beat; Meyer zu Schwabedissen, Henriette; Gatfield, John |
| Publication Year: |
2021 |
| Collection: |
University of Basel: edoc |
| Description: |
Immune mediated neuropathies are a group of heterogenous disorders affecting the peripheral nervous system. Characteristic for these diseases is the involvement of an immune response against autoantigens on axonal membranes or surrounding myelin. In a variety of peripheral neuropathies autoantibodies target glycan or peptide epitopes in the nodal and paranodal region. These polyneuropathies can have chronic or acute manifestations but generally respond to immunotherapies. Most treatment options however target the immune system unspecifically and can cause serious adverse effects. In some cases, patients do not respond to treatment or even show deterioration. In anti-MAG neuropathy and multifocal motor neuropathy the antigen-specific pathogenic autoantibodies have been well described and therapeutic intervention is aimed at reducing antibody levels or interfering with its effector functions. A recently developed glycopolymer-based therapeutic approach for the treatment of anti-MAG neuropathy (PPSGG) specifically targets these disease-causing autoantibodies by presenting multiple carbohydrate mimetic copies of its antigen on a biodegradable poly-L-lysine (PLL) scaffold. In this thesis we review the importance of a reduction of autoantibody levels for clinical improvement in anti-MAG neuropathy, discuss the mechanism of action of PPSGG, evaluate its safety profile, and develop new glycopolymers to treat related peripheral neuropathies and viral infections. Despite clinical evidence for the pathogenicity of anti-MAG IgM autoantibodies, the significance of antibody titers as a predictive factor for response to therapy remains controversial. Current literature does not provide conclusive evidence on the association between reduced anti-MAG IgM titers and clinical improvement of neuropathic symptoms. We performed a retrospective study to test our hypothesis that changes in antibody titers are correlated with clinical response in anti-MAG neuropathy patients. We included 50 studies involving 410 anti-MAG neuropathy ... |
| Document Type: |
thesis |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://edoc.unibas.ch/96032/1/Thesis_FINAL_edoc.pdf; Aliu, Butrint. Development of therapeutic glycopolymers for the treatment of peripheral neuropathies and viral infections. 2021, Doctoral Thesis, University of Basel, Faculty of Science.; urn:urn:nbn:ch:bel-bau-diss152052 |
| Availability: |
https://edoc.unibas.ch/96032/; https://edoc.unibas.ch/96032/1/Thesis_FINAL_edoc.pdf |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.F909FA68 |
| Database: |
BASE |