In News:

A new drug, Gantenerumab, has shown potential in slowing the progression of early-onset Alzheimer’s by significantly reducing the accumulation of amyloid plaques, a major indicator of the disease.

Alzheimer’s Disease Overview

• Alzheimer’s disease is a progressive neurodegenerative disorder, primarily impairing memory, thinking, and reasoning.
• It is the most common cause of dementia, accounting for 60–80% of all dementia cases globally.
• The disease is marked by the accumulation of amyloid beta plaques, which interfere with neuronal communication and trigger brain inflammation, eventually leading to cell death.

What is Early-Onset Alzheimer’s Disease (EOAD)?

• EOAD affects individuals below 65 years of age, comprising 5–10% of total Alzheimer’s cases.
• It progresses more rapidly and often strikes during a person’s prime working years.
• EOAD is strongly linked to genetic mutations in three genes: APP, PSEN1, and PSEN2, which result in overproduction of amyloid beta proteins.

Amyloid Plaques: The Disease Hallmark

• Amyloid plaques are clusters of misfolded amyloid beta proteins.
• These plaques disrupt brain function, contribute to inflammation, and kill neurons.
• They are central to the amyloid hypothesis, which posits that amyloid accumulation is a primary cause of Alzheimer’s progression.

Gantenerumab: A Potential Breakthrough

• Gantenerumab is a monoclonal antibody developed to target and eliminate amyloid beta plaques in the brain.
• It can cross the blood-brain barrier, a key obstacle in neurological drug delivery.
• The drug binds to amyloid plaques, signaling microglial cells (brain's immune cells) to break down and clear these plaques.
• This action may slow cognitive decline in early stages of the disease.

Recent Clinical Trial Findings

• A randomized, placebo-controlled trial involved 73 participants with rare inherited EOAD mutations.
• A subgroup of 22 asymptomatic participants showed reduced risk of symptom development from nearly 100% to 50% over eight years.
• Brain imaging confirmed a significant reduction in amyloid buildup.

Limitations and Risks

• Amyloid-related imaging abnormalities (ARIA) were observed in 53% of trial participants:
  • Brain swelling in 30%
  • Microbleeds in 27%
  • Iron deposits in 6%
• No major hemorrhages or deaths occurred, but side effects necessitate regular monitoring.
• The cognitive benefits were modest, and the drug is costly to produce, raising affordability concerns.
• The study had a small sample size and focused only on a rare genetic subset of EOAD.

Significance and Future Prospects

• Gantenerumab supports the amyloid hypothesis, alongside other drugs like lecanemab and donanemab.
• Despite its discontinuation in 2022 due to limited efficacy, new findings may revive interest in its development.
• The trial highlights the critical importance of early diagnosis and biomarker testing for timely therapeutic intervention.