Alzheimer’s disease is a degenerative brain disease and the most common form of dementia. It is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks. In most people with Alzheimer’s disease, symptoms first appear in their mid-60s. Estimates vary, but experts suggest that more than 5.5 million Americans may have Alzheimer’s disease.
Our efforts to advance the treatment of Alzheimer’s disease
For years research and drug development efforts for Alzheimer’s disease have focused on the plaques and tangles, made up of abnormal protein clusters, that build up in between nerve cells and are visible using brain imaging techniques in people diagnosed with Alzheimer’s disease. At Alector, we are challenging this approach based on the insight that a majority of the genetic mutations known to increase the risks of Alzheimer’s disease are in proteins that regulate the brain’s immune system. Leveraging genetics to identify and validate the points of intervention closely associated with disease pathology, we are developing novel therapeutics designed to improve the function of brain’s innate immune cells, the microglia, to slow the progression of neurodegenerative diseases like Alzheimer’s disease.
In our efforts to address Alzheimer’s disease with an immuno-neurology approach, we have initially focused on the targets TREM2 and SIGLEC3. TREM2 is part of a family of receptors referred to as triggering receptors expressed on myeloid cells (TREM) and is found on microglial cells in the brain. The role of TREM2 in Alzheimer’s disease was first discovered through large scale genome-wide association studies where it has been shown to have one of the most important genetic links to sporadic Alzheimer’s disease. Research suggests that reduction of TREM2 functionality may lead to Alzheimer’s disease and other forms of dementia. AL002 is intended to counteract this decreased functionality by optimizing TREM2 signaling to improve activity of the microglia to target multiple pathologies that are present in Alzheimer’s disease, rather than focusing on a single pathology.
A Siglec (sialic acid-binding immunoglobulin-like lectin) generates activating or inhibitory signals and plays an important role in neuroinflammation. Genomic studies have revealed that SIGLEC3 (also called CD33) is a risk factor for late onset Alzheimer’s disease and one variant of SIGLEC3 is thought reduce the ability of the microglia to clear amyloid plaques, contributing to disease progression. AL003 is intended to block the function of SIGLEC3 to increase microglia activity.
Alector’s clinical trials in Alzheimer’s disease
Alector is conducting clinical studies of AL002 and AL003 for the treatment of Alzheimer’s disease.