The tracers Lilly now has at its disposal include T-807 and T-808, compounds. Hartmuth Kolb and colleagues at Siemens, Los Angeles, formerly in Culver City, have begun testing in humans in a pilot program. Binding of these 18F-labeled tau ligands in the human brain seems to correlate with dementia progression (see ARF related news story). "One reason we think tau imaging is the next frontier is that the number and location of tau aggregates on autopsy correlate with the severity of disease," said Skovronsky. With the availability of specific tau ligands for use in people, that correlation can be tested in living patients, he said. The lack of a tight correlation between amyloid deposition and clinical symptoms of AD means it has taken researchers many years to understand its significance in AD pathogenesis (see ARF AD/PD news story). This kind of understanding could come faster with tau, researchers hope.

Skovronsky said Lilly will use these tau tracers in conjunction with their research and development program over the next few years. Tau imaging will complement the company's tau program, much like Amyvid has done for its development of Aβ therapeutics. "Our primary intent will be to develop treatments by better understanding tau pathology, tailored therapeutics, and tau potential as a surrogate marker for disease," said Skovronsky. He declined to speculate whether tau PET could piggyback on current and upcoming clinical trials for solanezumab, and Lilly’s β-secretase inhibitor LY2886721, including the DIAN (see ARF related news story) and A4 (see ARF related news story) prevention trials, and treatment trials for people with mild AD (see ARF related news story).

The tau tracers may also be useful for other neurodegenerative diseases characterized by tau aggregation. These include some frontotemporal dementias, corticobasal dementia, supranuclear palsy, Pick's disease, and even chronic traumatic encephalopathy, said Skovronsky. “We will fully characterize the spectrum of pathology in diseases with respect to the binding of these compounds,” he said.—Tom Fagan.