Gene silencing drug for Alzheimer's disease shows promise in safety trial

A new 'gene silencing' drug lowers levels of a harmful protein found in Alzheimer's disease, the during first treatment trial of its kind.

Alzheimer's disease is the most common cause of dementia, causing progressive memory loss in patients. The disease is associated with the build-up of two misfolded proteins known as amyloid beta and tau, which prevent neurons from communicating effectively within the brain. Researchers at University College London Hospital have developed a drug that targets the protein tau by silencing the tau gene known as MAPT.

'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,' first author and consultant neurologist Dr Catherine Mummery, from University College London Hospitals, said. '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.'

The study, published in Nature, details the first clinical trial to use a 'gene silencing' drug, named BIIB080, to prevent the MAPT gene from being translated into tau protein within the brain.

The phase 1 trial assessed the safety and dosage required for this new drug to influence MAPT expression levels. 46 patients were recruited, with the average age being 66, all diagnosed with mild Alzheimer's disease. The trial took place from 2017 to 2020, and neither the participants nor the researchers knew whether or not the patient was receiving the drug.

The trial saw a 50 percent reduction of the tau protein measured in patients who had received the highest dose after 24 weeks. No severe adverse effects were reported, with the most common side effect being a headache. However, the sample size for this trial was small and only included white participants. Future trials will need to be larger, recruiting a more diverse range of patients.

There are no FDA approved drugs that target tau within Alzheimer's disease, with BIIB080 being the first prospective drug to target dementia using a 'gene silencing' mechanism. As BIIB080 has passed safety concerns, future trials will look to see whether this drug has any clinical benefits.

'It's an incredibly exciting time in dementia research with each new finding bringing us closer to new treatments', Dr Susan Kohlhaas, executive director of research and partnerships at Alzheimer's Research, explained. 'Research like this shows just how vital clinical trials are if we're to make a real difference to the lives of people affected by dementia. With more work like this, research will pave the way towards a cure.'