A breakthrough 'gene silencing' Alzheimer's drug shows promise

London: UK scientists have conducted the first-ever trial of a new drug for Alzheimer's disease that is able to safely and successfully lower levels of the harmful tau protein known to cause the disease.

The trial, led by a team at the University College London, represents the first time that a "gene silencing" approach has been taken in dementia and Alzheimer's disease.

The approach uses a drug called BIIB080 (IONIS-MAPTRx) to "silence" the gene coding for the tau protein - known as the microtubule-associated protein tau (MAPT) gene.

This prevents the gene from being translated into the protein in a doseable and reversible way. It will also lower the production of that protein and alter the course of disease.

"We will need further research to understand the extent to which the drug can slow progression of physical symptoms of disease and evaluate the drug in older and larger groups of people and in more diverse populations," said consultant neurologist Dr. Catherine Mummery (UCL Queen Square Institute of Neurology & the National Hospital for Neurology and Neurosurgery.

"But the results are a significant step forward in demonstrating that we can successfully target tau with a gene silencing drug to slow - or possibly even reverse -- Alzheimer's disease, and other diseases caused by tau accumulation in the future," Mummery said.

The phase 1 trial looked at the safety of BIIB080, what it does in the body, and how well it targets the MAPT gene.

In all, 46 patients, with an average age of 66, were enrolled in the trial -- which took place from 2017 to 2020. The trial looked at three doses of the drug, given by intrathecal injection (an injection into the nervous system via the spinal canal), compared with the placebo.

The results, published in the journal Nature Medicine, show that the drug was well tolerated, with all patients completing the treatment period and over 90 per cent completing the post-treatment period.

Patients in both the treatment and placebo groups experienced either mild or moderate side effects -- the most common being a headache after injection of the drug. However, no serious adverse events were seen in patients given the drug.

The research team also looked at two forms of the tau protein in the central nervous system (CNS) -- a reliable indicator of disease -- over the duration of the study.

They found a greater than 50 per cent reduction in levels of total tau and phosphor tau concentration in the CNS after 24 weeks in the two treatment groups that received the highest dose of the drug.

There are currently no treatments targeting tau. The drugs aducanumab and lecanemab -- recently approved for use in some situations by the US Food and Drug Administration -- target a separate disease mechanism in AD, the accumulation of amyloid plaques.