Clinical

Treatment of Alzheimer’s

New antibodies developed by Uppsala University researchers may help treat Alzheimer’s disease more effectively in the future. It may be feasible to monitor the progression of the illness by creating antibodies that bind to even the smallest aggregation or clumps of amyloid-beta protein. It’s been tough to come up with viable treatments for Alzheimer’s disease. Some of the most potent drugs are so new that they are only having a little impact. It is because the antibodies employed do not attach to all kinds of toxic aggregates that cause Alzheimer’s disease that they are ineffective.

There are aggregates of the amyloid-beta protein in Alzheimer’s patients. The clusters formed as a result of this process are known as aggregates. A previous study conducted by the same team found that administering the peptide somatostatin caused the body to start breaking down aggregate-forming molecules. To block hazardous aggregates from damaging cells, the researchers in the current work used an antibody that can attach to them. It has been shown that antibodies have a significantly stronger affinity for big, rather than tiny, aggregates of tumor cells when used in current patient trials. Many people believe that tiny clusters are much more hazardous than big ones since they may move about so much more easily.

An antibody formulation was created for the present research with the goal of binding to both big and tiny aggregates of amyloid beta. Because of the avidity effect, antibodies are able to attach tightly to their targets. This necessitates the simultaneous binding of the antibody’s two arms to the same target. The antibody’s arm distance determines how tightly the antibody binds to a given aggregation. As long as the aggregate is larger than the distance between the arms, the arms will have a weaker bond to it. If the aggregate is bigger, they become very tightly bound to it. Researchers have created a novel antibody structure that has shorter distances between the arms and binds to smaller aggregates, as detailed in a new study published online today. More binding sites in the new format mean that the binding is much stronger.

“The novel antibody shape has a 40-fold increase in binding strength due to the avidity effect. Additionally, the new kind of antibody has the ability to avidly bind tiny aggregates, something no other antibody has been able to accomplish before. That’s incredible, “Greta Hultqvist, the study’s principal investigator and senior lecturer at Uppsala University’s department of Protein Drug Design. This novel antibody format was shown to protect cells against amyloid-beta aggregate-induced cell death in a cell culture experiment. Despite the lack of pre-clinical testing, the researchers believe their findings indicate that the novel antibody design may be more successful than others that have been tested before. “However, the novel antibody design may be used to target additional disease-causing aggregates than amyloid-beta in Alzheimer’s disease. The novel format may potentially offer new therapeutic options for illnesses like Alzheimer’s and Parkinson’s where proteins start to congregate over time, therefore this is something we’re looking forward to in the long run “Fadi Rofo, a doctorate candidate and the study’s lead author, agrees.

Reference : Fadi Rofo, Jos Buijs, Ronny Falk, Ken Honek, Lars Lannfelt, Anna M. Lilja, Nicole G. Metzendorf, Tobias Gustavsson, Dag Sehlin, Linda Söderberg, Greta Hultqvist. Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid betaTranslational Neurodegeneration, 2021; 10 (1) DOI: 10.1186/s40035-021-00258-x

Categories: Clinical