FDA-Approved Drug Slows Down Alzheimer’s: The Mechanism Revealed
Alzheimer’s disease is a complex and devastating neurodegenerative disease that affects millions of people worldwide. Unfortunately, there is currently no cure. However, there is some good news. Lecanemab, an FDA-approved drug, has shown promising results in slowing down cognitive decline in early-stage Alzheimer’s patients. Until recently, it was unclear how this drug worked, but new research from the Rockefeller University in New York has shed some light on its mechanism of action.
Neurobiologist Erin Norris explains, “We believe we’ve found a mechanism that is one of the reasons lecanemab works.” The drug appears to inhibit the plasma contact system, which is an interaction between proteins in the blood that promotes clotting and inflammation. While this system is essential for repairing tissue damage, overstimulation in sensitive areas like brain tissue can lead to pathologies such as Alzheimer’s disease. By blocking the contact system, lecanemab reduces Alzheimer’s pathology.
Alzheimer’s disease is characterized by the clumping of two types of proteins, tau and amyloid beta (Aβ), into tangles and plaques in the brain. Of these plaques, protofibrils are considered the most toxic form. Lecanemab specifically targets these protofibrils. In an 18-month trial, patients who tooklecanemab had a significant reduction in amyloid beta plaque compared to those who took a placebo. It also slowed cognitive decline by 27 percent.
However, like any medication, lecanemab does have some adverse effects. Patients taking lecanemab have an increased risk of mild to moderate brain bleeds and swelling called amyloid-related imaging abnormalities (ARIA). Despite these risks, lecanemab has a lower ARIA rate compared to other similar plaque-busting therapies.
To understand why lecanemab is so effective, the research team analyzed plasma from donors without Alzheimer’s and found that protofibrils are the only form of Aβ that activates the plasma contact system. This activation leads to the overproduction of a peptide called bradykinin, which can cause the ARIA side effects. Lecanemab works by preventing protofibrils from activating the contact system, thus reducing bradykinin production.
Based on their findings, the research team has developed an antibody called 3E8, which targets a circulating plasma protein with a similar outcome. They believe that 3E8 has the potential to treat Alzheimer’s disease, either alone or in combination with medications like lecanemab. Furthermore, their research suggests that dysregulation of the contact system is involved in various other diseases such as COVID, sickle cell anemia, hereditary angioedema, inflammatory bowel disease, sepsis, lupus, arthritis, and even cancer metastasis.
While this research is promising, there is still a long way to go. Clinical trials will be needed to determine the efficacy and safety of 3E8 and its potential use in treating other diseases. Nonetheless, these findings provide hope for the development of new treatments for Alzheimer’s and other related conditions.
Keywords: FDA-approved drug, Alzheimer’s, lecanemab, cognitive decline, amyloid beta buildup, plasma contact system, protofibrils, Aβ plaques, clinical trials, 3E8 antibody, bradykinin, ARIA side effects, neurodegenerative diseases, treatment options.