Lanabecestat

Lanabecestat

Lanabecestat (formerly known as AZD3293 or LY3314814) is an experimental drug that was under investigation for the treatment of Alzheimer's disease. Lanabecestat is a BACE1 inhibitor, a type of drug that aims to inhibit the production of amyloid beta peptides, which are believed to play a critical role in the development and progression of Alzheimer's disease. Despite initial promise, the development of Lanabecestat was discontinued in 2018 after it failed to demonstrate efficacy in clinical trials.

Development and Clinical Trials

Lanabecestat was developed through a collaboration between AstraZeneca and Eli Lilly and Company. It was designed to target and inhibit BACE1, an enzyme involved in the production of amyloid beta peptides. By inhibiting this enzyme, Lanabecestat aimed to reduce the accumulation of amyloid plaques in the brain, which are a hallmark of Alzheimer's disease and are thought to contribute to the disease's progression.

Clinical trials for Lanabecestat included Phase I, Phase II, and Phase III studies. The Phase III studies, known as AMARANTH and DAYBREAK-ALZ, were designed to evaluate the drug's efficacy, safety, and tolerability in patients with early and mild Alzheimer's disease. However, in June 2018, AstraZeneca and Eli Lilly and Company announced the discontinuation of these trials. The decision was based on recommendations from an independent data monitoring committee, which concluded that the drug was unlikely to meet the primary endpoints of the studies.

Mechanism of Action

Lanabecestat functions as a BACE1 inhibitor. BACE1, or beta-site APP-cleaving enzyme 1, plays a key role in the production of amyloid beta peptides by cleaving the amyloid precursor protein (APP). The accumulation of amyloid beta peptides leads to the formation of amyloid plaques, which are toxic to neurons and are implicated in the cognitive decline associated with Alzheimer's disease. By inhibiting BACE1, Lanabecestat aimed to reduce the production of amyloid beta peptides and, consequently, the formation of amyloid plaques.

Discontinuation

The discontinuation of Lanabecestat's development was a significant setback in the search for effective treatments for Alzheimer's disease. The failure of Lanabecestat and other similar BACE1 inhibitors has led researchers to reevaluate the amyloid hypothesis and explore other potential targets and strategies for treating Alzheimer's disease.

See Also

• Alzheimer's disease
• Amyloid hypothesis
• BACE1
• Drug development