With the shine of amyloid fading, tau is a rising star in Alzheimer’s

This audio is auto-generated. Please let us know if you have feedback.

Sonya Miller follows the science. In 2017, she followed it so completely and with such focus into a crowded conference room that she accidentally sat next to the CEO of TauRx Pharmaceuticals and talked herself into a job.

Sonya Miller

TauRx medical oversight lead Sonya Miller

Permission granted by TauRx/Sonya Miller

That’s when Miller, an anesthetist for 25 years, was working as a principal investigator for several neuroscience trials, one of which was an Alzheimer’s disease study being conducted by TauRx, and she attended a presentation during the contempt meeting held by the company.

“I’m blind as a bat and I’m always late, and the only spot free was right at the front on the side,” Miller says. “I was actually next to Claude [Wischik, TauRx CEO] and John Cheung, who’s head of development, and I was telling them all the things that were wrong with the trial — and I didn’t have a clue.”

It turned out one of the missing factors they needed was a doctor to head up the company’s trials. Miller was hired as medical oversight lead, and now she also holds the position of head of medical affairs at TauRx.

“Trails are often long and winding and interesting, aren’t they? It suited me,” Miller says. “I wouldn’t work in a massive pharma where things get shut down because of funding or current trends — TauRx is completely focused on neuroscience and always has been, and it’s completely science driven.”

Miller says TauRx “is really an R&D company that is now becoming more than that, but the science has always been pivotal.”

TauRx plans to release interim results from its phase 3 study in Alzheimer’s later this month. The study is comparing the company’s tau aggregation inhibitor to a placebo for 12 months, and then a year from now, comparing that to people who have had the drug for a total of two years.

A product of almost 30 years of research, TauRx’s potential treatment breaks up the sticky tangle of proteins that build up inside neurons and are linked to Alzheimer’s disease. The results of the trial could set the stage for the importance of tau in the therapeutic landscape and ultimate treatment of patients with the devastating condition.

The company is also developing an anti-synuclein compound for Parkinson’s disease and earlier-stage candidates for other neurodegenerative conditions.

Tau’s promise

Normally, tau is critical to communication between brain cells, but misfolding of the protein causes the tangles, which disrupt brain function.

“These good proteins go bad for a variety of reasons and they become larger and larger until they clump and tangle and destroy the nerve cell function,” Miller says. “And this process continues and accelerates, and at a certain point it’s like falling off a cliff face, and you deteriorate very rapidly.”

Alzheimer’s can lead to a patient’s death as the result of a loss of brain volume or injury due to a lack of awareness.

“Our focus has always been on tau, and we were considered sort of the outrider early on.”

Sonya Miller

TauRx Pharmaceuticals medical oversight lead

In Alzheimer’s research, tau is one of two leading biomarkers for the disease, the other being amyloid plaques that also build up in the brain. While tau aggregates inside the neurons, amyloid collects outside the cells.

The search for either amyloid plaques or tau in patients is often driven by external factors like availability of testing and scanning, Miller says, and the specific substances — called radioligands — used to scan for amyloid plaques were developed much earlier than those for tau.

“Tau is really only becoming more mainstream now,” Miller says. “All the last 20 years of research, it was more focused on amyloid, and that was more because you could scan and you could see amyloid in the brain lit up with radioligands.”

It stands to reason that researchers more quickly developed drugs reducing the amount of amyloid plaque buildup, but this didn’t always lead to a change in cognitive function, Miller says. The most recent example of this can be seen in the controversial approval of Biogen and Eisai’s Aduhelm, which did reduce amyloid plaque but had conflicting clinical outcomes in late-stage studies.

Leave a Comment