Pioneering ‘gene silencing drug’ for Alzheimer’s disease shows promise

June 15, 2023 | Histopathology

Researchers from the University of London and UCLH conducted a world-first trial of a new genetic therapy that is able to safely and efficiently decrease levels of harmful tau protein known to cause Alzheimer’s disease.

This gene silencing approach uses BIIB080 (/IONIS-MAPTRx), a drug classified as an antisense oligonucleaotide which stops the RNA from producing a protein. This drug silences the MAPT (microtubule-associated protein tau) gene, the coding required for the production of tau. This in turn prevents the gene from being translated and alters the course of disease.

From 2017 to 2020, Phase 1 trials were conducted on 46 patients with the average age of 66 and results showed indication of this method having a biological effect. They looked at the safety of BIIB080, how it affects the body, and how successful it is in targeting the MAPT gene. They administered the drug in three doses via intrathecal injection. Reports show that the drug was well-tolerated with 90% of the patients completing the post-treatment period. However, mild to moderate side effects such as headache have been observed both in treatment and placebo groups though no adverse events were noted.

Over the duration of the study, the team examined two forms of tau protein. They discovered that those who received the highest dosage showed greater than 50% reduction in total tau and phosphor tau levels after 24 weeks.

Researchers have to perform trials on larger groups and a more diverse population of patients to confirm whether it leads to significant clinical benefits and to understand the extent to which the drug is able to slow the disease’s progression.