The new Alzheimer’s drug may be able to delay the inevitabilities of Alzheimer’s, but we are still far from a cure.
The Food and Drug Administration granted full approval to lecanemab (brand name Leqembi) for treating adults with Alzheimer’s disease this month — suggesting that the drug should be used for patients experiencing mild dementia.
Alzheimer’s is a progressive neurological disease that causes memory loss, language problems, changes in mood, and other forms of cognitive decline.
Details: Lecanemab, manufactured by Japanese drugmaker Eisai and Biogen, is currently suggested to reduce the rate of cognitive decline in the early stages of Alzheimer’s disease.
Data-driven: A clinical trial of 1795 patients involved a lecanemab group and a placebo group, with the lecanemab group receiving 10 mg per kilogram of body weight of the drug intravenously once every 2 weeks.
Side effects: While patients experiencing side effects may not have some obvious symptoms, people being treated with lecanemab would require regular brain scans to rule out possible swelling of the brain.
Expert opinions: Science has searched for an effective treatment for Alzheimer’s for a while and previously promising drugs have flamed out, which raises concern over this new approval. Both patients and doctors are skeptical about the future of lecanemab, especially due to its high price and the extensive patient testing it implies.
Succumbing to the cognitive decline that occurs due to Alzheimer’s disease can be an increasingly painful experience, but science is yet to decode what goes on inside the body causing such brain degeneration.
Alzheimer’s disease is not an inevitable consequence of aging, even if the two factors may be deeply correlated — with the prevalence of AD doubling every 5 years after age 65. The most widely hypothesized cause behind the disease are growths in the brain known as “beta-amyloid plaques.”
These plaques are toxic clumps of beta-amyloid proteins that multiply and stick together, forming insoluble plaques that block intercellular signaling and trigger inflammation — disrupting normal cellular functions. While these plaques physically change the brain, these alone aren’t what lead to the development of AD.
As Alzheimer’s disease progress with time, plaques, neurofibrillary tangles composed of tau proteins, and inflammation collectively result in irreversible neuronal damage and cognitive decline.
However, the amyloid hypothesis has recently also been on the receiving end of some controversy, as a report published in Science last year suggested that a 2006 study falsified some of the facts regarding a specific type of amyloid causing Alzheimer’s disease.
Two hallmark pathological features of Alzheimer’s disease are the accumulation of beta-amyloid plaques and tau protein tangles in the brain. The complex interplay of these rogue proteins has been known to disrupt synapses, cause inflammation of the brain, and eventually result in nerve cell death and severe dementia.
Image by National Institute on Aging
Lecanemab is a humanized monoclonal antibody that targets these beta-amyloid proteins that are known to aggregate to form plaques in the brain — believed to be one of the primary drivers of AD.
“The unusual thing about this drug is that it targets not only the amyloid plaques that are a hallmark of Alzheimer’s but also clumps of amyloid, called oligomers, that float around inside and between brain cells, along with protofibrils that share properties of both oligomers and plaques,” told neurologist Samuel Gandy to Scientific American.
The clinical trial suggested that while people getting lecanemab still experienced cognitive decline, it progressed 27 percent slower than those on a placebo.
Scientists suggest that drugs like aducanumab failed because they bind to amyloid protein after it clumps together to form plaques, whereas lecanemab interferes with them at an earlier stage, targeting the “protofibrils” of beta-amyloid — strands that have not yet aggregated to form plaques.
What’s next: Lecanemab can have some potentially life-threatening side effects, and the drug may also be less effective in slowing cognitive decline in women — with a supplementary appendix suggesting that the drug slowed cognitive decline in women by 12 percent compared to 43 percent in men.