This story was published as part of the 2024 Travel Fellowship Program to AAAS organized by the NASW Education Committee, providing science journalism practice and experience for undergraduate and graduate students.
Story by Soumilee Chaudhuri
Mentored and edited by Czerne M. Reid
DENVER — The FDA's July 2023 approval of a new drug to treat Alzheimer's disease marked important progress in a long quest. Dementia drug lecanemab, the first of its kind to earn that FDA honor, modifies underlying processes involved in the development of Alzheimer’s disease (AD), rather than just addressing symptoms.
“The ability to precisely target one of the defining pathological features of Alzheimer’s disease in the brains of AD patients is a scientific milestone,” said neurologist Madhav Thambisetty, a senior clinical investigator with the National Institute on Aging.
During a Feb. 17 session at the American Association for the Advancement of Science (AAAS) annual meeting, Thambisetty discussed the clinical promise and pitfalls of the new disease-modifying drug for millions of people affected by Alzheimer’s.
Though not likely to be effective against advanced dementia, the drug, marketed as Leqembi, has shown modest benefit for patients with early Alzheimer’s disease and mild cognitive impairment.
Alzheimer's is a severe form of dementia that slowly impairs memory and thinking, interfering with even simple day-to-day activities. It affects 1 in 9 people aged 65 and older in the United States, and 14 million will have it by 2060, according to estimates from researchers at the Centers for Disease Control and Prevention.
Alzheimer’s disease is linked to multiple risk factors such as genetics, environment, lifestyle and, most strongly, age. Accumulation in the brain of a type of protein called amyloid beta — leading to the formation of plaques — is thought to be an early toxic event that triggers a cascade of complex dysfunction, ultimately leading to cognitive decline.
Amyloid beta protein is the target of the new drug, which is an antibody that binds to the toxic plaques, allowing the immune system to remove them from the brain, slowing the disease.
Cognitive decline slowed by almost 30% among patients with early stage disease who were treated with Leqembi over 18 months. The clinical trials to test the drug’s safety and effectiveness involved 1,800 participants.
Leqembi’s success comes after decades during which clinical trials of other Alzheimer's drugs were discontinued because of failure to show significant benefit, risky side effects, inappropriate dosage or other factors.
Results from the new drug demonstrate that successful treatment is possible for neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s that are associated with protein abnormalities in the brain, said University of California, San Francisco Alzheimer’s researcher Dr. Michael Weiner, by email.
To be eligible for treatment with Leqembi, patients must undergo brain scans to confirm buildup of amyloid beta in the brain. Medical experts also recommend ongoing psychological support and consultation with providers.
“The risk benefit ratio is very different in different patients,” Weiner said by email. Effects vary with age, brain imaging results, whether or not a patient is taking blood thinners, and the variant of an Alzheimer’s-related gene called apolipoprotein E, or APOE, that is present. “Patients and their families should learn what they can from the internet and be prepared with questions when they see their physician,” he said.
Despite its potential benefits, Leqembi does not cure Alzheimer’s disease. And it comes with complex side-effects. Those include a condition called ARIA, short for amyloid-related imaging abnormalities, involving bleeding, swelling, or atrophy of the brain. Three patients participating in clinical testing of Leqembi reportedly died. The FDA requires a "black box" warning label on the drug, alerting users to possible adverse reactions that can lead to serious injury or death.
These side effects are the main remaining obstacle to widespread use of the drug, since other necessary parts — FDA approval, the agreement of public and private insurers to pay for the therapy, and provisions made by health care providers to administer it — are now in place, experts say.
Understanding how the harmful side effects occur in the body and why some patients are at greater risk than others, could allow fine-tuning of the new drug and speed research on less costly therapies with fewer side effects. Research also continues on ways to develop drugs that work not just after Alzheimer's has already developed, but before.
Soumilee Chaudhuri is a Ph.D. candidate at Indiana University School of Medicine, studying the impact of lifestyle risk factors on Alzheimer’s and dementia. She writes for Brainpost, and founded IMPACT Indiana, an initiative to engage early career trainees in reciprocal conversations about dementia research and prevention with community members and policymakers. She volunteers as a patient advocate with the Alzheimer’s Association. Follow her on Linkedin and X or email her at soumilee2012@gmail.com. Read about her work in dementia, public health and science communication: https://www.soumileechaudhuri.com.
Edited by: Czerne M. Reid
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