After cells make tau, it can be modified in many ways. It can be cut into smaller pieces. Other molecules can attach themselves to tau. Then, individual proteins can start sticking together into larger and larger clumps of tau, accounting for the many different forms tau can take.
Finding the rest of the story
Until recently, much of the focus in the discovery and development of new medicines for Alzheimer’s has been the amyloid plaques associated with the disease. Unfortunately, the majority of these approaches have failed to slow progression of the disease in human clinical trials.
“The failure of these approaches has freed the field to embrace and explore new approaches, including tau targeting, and the science is advancing in different ways,” says Lynne Rueter, Ph.D., director of neuroscience discovery at AbbVie.
Having identified that it is tau spreading that causes neurodegeneration, one approach to research includes focusing on targets in the brain that might help to reduce the spread.
Another approach targets tau, itself. “We are trying to stop tau pathology and are testing molecules that isolate and target specific tau forms, as well as those that have pan-tau activity,” Rueter says. “One program at AbbVie is that of ABBV-8E12, an antibody in Phase 2 development that interacts with both soluble and insoluble forms of the protein, which will allow us to see the impact of blocking tau spread on disease progression.”
Impact beyond Alzheimer’s
Tau is not just found in Alzheimer’s disease. Tau-associated neurodegeneration is found in other neurodegenerative diseases, including progressive supranuclear palsy, Huntington’s disease and others.
“The link between tau and neurodegeneration is so strong that I am 100 percent confident that we have the right target,” Langlois says. “And when we figure out how to target it effectively, we may be able to rewrite the ending of the story for patients with Alzheimer’s disease and beyond.”