The search to prevent Alzheimer’s
Investigators are testing a new drug for its potential to slow and prevent the disease
By Jessica Binkley Lain
Alzheimer’s disease continues to challenge medical science with its complex and devastating effects on cognition and memory. In a significant stride forward, the Food and Drug Administration recently approved lecanemab as a promising new compound found to slow the progression of the disease. Researchers at The University of Texas Health Science Center at San Antonio are now diving deeper into the mechanisms of lecanemab to determine if this innovative drug also has preventive potential.
What happens in the brain Lecanemab is a humanized monoclonal antibody that removes amyloid buildup, which is a protein that is one of the key features of Alzheimer’s disease. The antibodies bind to and clear away the amyloid that builds up in the spaces between the neurons, which hinders the messages buzzing from synapse to synapse throughout the brain.
This amyloid protein starts building up in the brain about 20 years before the first symptoms of Alzheimer’s emerge. As amyloid accumulates, an abnormal form of a second protein, called tau, also starts to build up, and the buildup of this abnormal tau can kill the neurons.
“The location of where these neurons die in the brain seems to determine the symptoms a patient will experience,” explained Sudha Seshadri, MD, director of the university’s Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases.
“If the neurons die in the part of the brain that is responsible for making new memories, then memory issues will be the symptom. If it’s a part of the brain that’s responsible for communication, then you may see primary progressive aphasia. If it’s mostly in the posterior cortex of the brain, then a patient may have difficulty making sense of what they see,” Seshadri said.
In a 2019 study called Clarity AD, lecanemab was shown to reduce the amyloid burden to a level that is seen in healthy brains. This is a highly effective treatment in slowing disease progression, but it can’t undo the damage of neuronal death in the brain, explained Seshadri.
“This type of treatment doesn’t typically bring back function that has already been lost, but it does slow down the decline,” Seshadri said. “That’s why we’re looking at the effects of removing amyloid buildup in earlier stages of the disease, before function is lost.”
Tracking amyloid levels
Currently, the health science center is part of a national, multisite study called AHEAD 3-45. The ongoing study investigates lecanemab’s effects when administered before the onset of symptoms, at the preclinical stage of the disease. The findings of this study will have significant impacts on potential preventive treatment.
“We want to see if completely asymptomatic, cognitively normal people who have excess amyloid in the brain will benefit from receiving lecanemab,” Seshadri said.
The study will span five years, with participants undergoing regular positron emission tomography scans and infusions of lecanemab to observe and track the amount of amyloid in the brain.
How often a participant receives the treatment depends on how much amyloid is found in their scan when they begin, Seshadri explained.
“We don’t know if lecanemab works at this stage, but if it does work in the preclinical stage of the disease — if we find that it can delay or prevent the development of cognitive symptoms — that will be a very remarkable achievement,” Seshadri said. “We’d actually be preventing Alzheimer’s, which is a huge step.”
