Probing the Role of Tau Protein in Disease

Researchers at the Society for Neuroscience conference discuss tau’s contributions to epilepsy, Alzheimer’s disease, and other tauopathies.

By | November 17, 2016

tau tanglesNeurofibrillary tangles of tau protein in the hippocampus of an old person with Alzheimer’s-related pathologyWIKIMEDIA, PATHOFor nearly a decade, researchers have recognized that tau proteins regulate neural networks. The protein, which stabilizes microtubules in the cell, correlates with the sort of neuronal hyperexcitability often seen during seizures. Tau also appears to interact with amyloid-β peptides to affect seizure frequency and severity in mouse models of Alzheimer’s disease.

Based on these and other findings, many groups have started to test the effects of lowering tau levels in mouse models, and so far, the results show promise. “Tau reduction has protective effects in neural excitability,” reducing severity of seizures in epileptic mice, for example, Erik Roberson of the University of Alabama at Birmingham said this week (November 15) at the Society for Neuroscience conference in San Diego, California. “How can these protective effects be harnessed for the therapy of human diseases?”

Antisense oligonucleotides are an increasingly popular way to target tau. A handful of biotech and pharma companies already have antisense oligonucleotides, synthetic polymers that bind endogenous nucleic acids, that target tau on their shelves, and early-stage clinical work has shown promising safety profiles. “We became very excited that tau antisense oligonucleotides could be a rapid way to get into the clinic,” said Bristol-Myers Squibb’s Angela Cacace, who has tested the effects of a tau-targeting oligonucleotide for the treatment of a tauopathy called progressive supranuclear palsy, a degenerative brain disease.

Meanwhile, Biljana Djukic of Lennart Mucke’s lab at the Gladstone Institutes is also testing anti-tau antisense oligonucleotides, in this case, for another tauopathy known as Dravet syndrome. So far, mouse studies have shown dramatic reductions in early mortality. “Nothing has shown that level of effect [in preventing death],” Mucke said. “There’s something very interesting about tau.”

Stay tuned for The Scientist’s December issue for a Bio Business feature story on the variety of oligonucleotide therapies, which are being hailed as the third major drug class after small molecules and biologics, that are now making their way through late-stage clinical development.

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