World's first 'gene silencing' Alzheimer's drug

The first study of a brand-new Alzheimer's medicine that can successfully and safely reduce levels of the dangerous tau protein known to be the disease's aetiology was carried out by UK researchers.

The trial, which is being run by a group at the University College London, is the first to use a "gene silencing" strategy for dementia and Alzheimer's disease.

The strategy "silences" the tau protein-coding gene, also known as the microtubule-associated protein tau (MAPT) gene, using the medication BIIB080 (IONIS-MAPTRx).

As a result, the gene cannot be translated into a protein in a dose- and reversible-dependent manner. Additionally, it will decrease the manufacturing of that protein and change how a disease develops.

According to consultant neurologist Dr. Catherine Mummery (UCL Queen Square Institute of Neurology & the National Hospital for Neurology and Neurosurgery), "We will need more 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 as well as in more diverse populations."

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

The safety of BIIB080, its physiological effects, and its effectiveness in targeting the MAPT gene were all examined in the phase 1 trial.

The experiment, which ran from 2017 to 2020, involved a total of 46 individuals, with an average age of 66. Three dosages of the medication were injected intrathecally (via the spinal canal into the nerve system) in the trial, and they were compared to a placebo.

The findings, which were reported in the journal Nature Medicine, demonstrate that the medication was well tolerated, with every patient finishing the course of therapy and more than 90% finishing the post-treatment phase.

Both the treatment and placebo groups of patients reported mild to severe adverse effects, with headaches following medication injection being the most frequent. Patients who received the medication, however, reported no major negative side effects.

Over the course of the investigation, the research team also examined two variants of the tau protein in the central nervous system (CNS), which is a trustworthy sign of disease.

After 24 weeks, the two treatment groups that got the highest dose of the medication showed a higher than 50% drop in the levels of total tau and phosphor tau concentration in the CNS.

There are no therapies available now that target tau. Accumulation of amyloid plaques is a distinct disease process in AD that is the focus of the medications aducanumab and lecanemab, which the US Food and Drug Administration has licenced for use in certain circumstances. [IANS/JS]