Skip to main content
Premium Trial:

Request an Annual Quote

Alzheimer's Disease Treatment Lecanemab Blocks Plasma Contact System, Study Finds

Rockefeller University researchers have unraveled a molecular mechanism through which Leqembi (lecanemab), an anti-amyloid drug developed by Biogen and Eisai, might have its therapeutic effect in Alzheimer's disease (AD). Leqembi, which has a list price of $26,500 a year, first received an accelerated approval, since  converted to a full approval, from the US Food and Drug Administration based on the surrogate endpoint that it clears amyloid plaques. In a new study in the Proceedings of the National Academy of Sciences, the Rockefeller researchers write that toxic beta-amyloid (Aβ) protofibrils, thought to be a major driver of AD, activate a molecular cascade called the plasma contact system, potentially leading to the vascular and inflammatory abnormalities associated with AD. Using western blotting, chromogenic assays, and other approaches, the authors found that Aβ protofibrils are more effective activators of the human plasma contact system than other Aβ forms, such as monomers, intermediate-length oligomers, and fibrils. The authors further found that Aβ protofibrils accelerate activation of the plasma contact system by binding to coagulation factor XII (FXII) and high-molecular-weight kininogen (HK). Lecanemab, they note, works by blocking the binding of FXII and HK to Aβ and prevents Aβ protofibril-mediated acceleration of blood clotting in normal human plasma. Moreover, lecanemab's effective blocking of the contact system could reduce bradykinin production and, therefore, reduce the occurrence of amyloid-related imaging abnormalities in AD patients, the researchers say.

 

The Scan

Positive Framing of Genetic Studies Can Spark Mistrust Among Underrepresented Groups

Researchers in Human Genetics and Genomics Advances report that how researchers describe genomic studies may alienate potential participants.

Small Study of Gene Editing to Treat Sickle Cell Disease

In a Novartis-sponsored study in the New England Journal of Medicine, researchers found that a CRISPR-Cas9-based treatment targeting promoters of genes encoding fetal hemoglobin could reduce disease symptoms.

Gut Microbiome Changes Appear in Infants Before They Develop Eczema, Study Finds

Researchers report in mSystems that infants experienced an enrichment in Clostridium sensu stricto 1 and Finegoldia and a depletion of Bacteroides before developing eczema.

Acute Myeloid Leukemia Treatment Specificity Enhanced With Stem Cell Editing

A study in Nature suggests epitope editing in donor stem cells prior to bone marrow transplants can stave off toxicity when targeting acute myeloid leukemia with immunotherapy.