A world-first trial at UCL and UCLH has found a new gene therapy for Alzheimer’s disease that can safely lower levels of the harmful tau protein known to cause the disease. Led by consultant neurologist Dr. Catherine Mummery, the trial represents the first time a “gene silencing” approach has been taken in dementia and Alzheimer’s.
The trial uses a drug called BIIB080 (/IONIS-MAPTRx), which is an antisense oligonucleotide (used to stop RNA producing a protein), 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 the disease.
The phase 1 trial looked at the safety of BIIB080, what it does in the body, and how well it targets the MAPT gene. It involved the UCL Dementia Research Centre, was supported by the NIHR UCLH Biomedical Research Centre, was supported by the NIHR UCLH Biomedical Research Centre, and took place at the Leonard Wolfson Experimental Neurology Centre at NHNN.
Around 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, compared with the placebo. Results show that the drug was well tolerated, with all patients completing the treatment period and over 90% completing the post-treatment period.
Dr. Mummery said, "We will need further research to understand the extent to which the drug can slow the progression of physical symptoms of disease and evaluate the drug in older and larger groups of people and in more diverse populations. 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.”