Gamma antibodies against diabetes and Alzheimer's and Parkinson's diseases
The appearance of symptoms of these diseases is associated with abnormal aggregation of proteins into conglomerates that are toxic to brain cells (Alzheimer's and Parkinson's diseases) and pancreas (type 2 diabetes mellitus). Antibodies – proteins used by the immune system to kill bacteria and viruses – are a potential weapon in the fight against toxic protein particles. However, the effectiveness of traditional therapeutic antibodies is limited by their low binding capacity: one antibody is able to bind no more than two protein molecules at the same time.
Specialists of the Rensselaer Polytechnic Institute, working under the guidance of Professor Peter Tessier, have developed a new process that allows to obtain antibodies, each of which can bind up to 10 target protein molecules. Even a small concentration of such antibodies prevents the formation of toxic protein aggregates. This ability is extremely important in the treatment of neurodegenerative diseases, since less than 5% of the antibodies injected into the bloodstream penetrate into the brain.
The unprecedented high binding capacity of the new antibodies is due to a new method of their production, which is based on the same molecular interactions that lead to the formation of toxic protein particles.
Traditionally, antibodies are obtained by injecting mice with a target protein that triggers the production of antibodies specific to it. The method developed by Tessier's collaborators is based on the embedding of small peptides (6-10 amino acid residues) that are representative of proteins associated with the diseases listed above (beta-amyloid, alpha-synuclein and insular amyloid polypeptide) into certain regions of single-domain antibodies.
The resulting so-called "gamma bodies" prevent the formation of amyloid aggregates by converting peptide monomers and/or intermediate fibrous structures into small unstructured complexes that do not have toxicity. The developers believe that in the future such antibodies can be used as aggregation inhibitors and other amyloidogenic polypeptides associated with human diseases.
Article by Ali Reza A. Ladiwala et al. Rational design of potential domain antibody inhibitors of amyloid fibril assembly is published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Rensselaer Polytechnic Institute:
Novel Antibodies for Combating Alzheimer’s and Parkinson’s Disease.
07.12.2012