Gene-blocking therapy reverses Alzheimer’s-like symptoms in mice

Targeting tangles of tau protein in mice with Alzheimer’s-like symptoms has reversed their brain damage, halting memory loss and extending their lives. 

Clumps of two types of sticky protein build up in the brains of people with Alzheimer’s disease: beta-amyloid plaques, and tangles of tau. While many attempts to develop drugs to treat Alzheimer’s have targeted beta-amyloid, tau protein tangles have long been suspected to play a role in memory loss.

“Tau is what correlates with memory problems, so one hypothesis is that lowering tau could be beneficial,” says Tim Miller of Washington University in St Louis, Missouri.

Now Miller’s team has purged tau tangles from the brains of Alzheimer’s-like mice for the first time. They used fragments of RNA called antisense oligonucleotides to sabotage the gene that makes tau, preventing it from being fully translated into protein.

Once a day for four weeks, the team injected the antisense treatment, named Tau-ASO12, into the fluid at the base of each mouse’s spine. The mice had been genetically engineered to make a rogue form of tau similar to what is seen in people with Alzheimer’s, predisposing the mice to developing tau-related brain problems.

The drug successfully spread throughout the brain, and was linked to a reduction in levels of tau that was made. It also seemed to destroy existing tau tangles, and prevent tau from spreading around the brain in older mice.

Overall, mice that got Tau-ASO12 lived up to 50 days longer than those that didn’t, and were able to retain important abilities, such as nest-making skills, that were lost in mice that received a sham treatment.