A new strategy against Alzheimer’s disease that consists of ‘silencing’ the gene that encodes the tau protein – whose high levels in the brain are considered a cause of the neurodegeneration suffered by those affected – has shown its safety and efficacy in a clinical trial in phase 1 in which 46 patients with an average age of 66 years participated.
The trial was led by Dr. Catherine Mummery, a consultant neurologist at UCL (University College London) Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, together with colleagues from University College London Hospital (UCLH), and in it A ‘gene silencing’ approach has been followed for the first time to combat dementia and Alzheimer’s.
In this new gene therapy, a drug called BIIB080 (/ IONIS – MAPTRx) has been used, which is an antisense oligonucleotide that prevents RNA from producing a protein and has been used to ‘silence’ the gene that encodes the tau protein, known such as microtubule-associated protein tau gene or MAPT gene. In this way, the gene is prevented from being translated into the protein in a measurable and reversible way, and it will also reduce the production of that protein and modify the course of the disease.
The results go a long way toward showing “that we can successfully target tau with a gene-silencing drug to delay, or possibly even reverse, Alzheimer’s disease.”
The study was carried out between 2017 and 2020 and compared the effects of three doses of the drug, given by intrathecal injection (an injection into the nervous system through the spinal canal) with placebo. Their results have been published in Nature Medicine and indicate that this technique has a biological effect, although it has only been tested in 46 patients.
More than 50% reduction in tau protein levels
The investigators found that the drug was well tolerated, with all patients completing treatment and more than 90% completing the post-treatment period. The reported side effects were mild or moderate, both in the treatment group and in the placebo group. The most common adverse effect was headache after drug injection, but no serious adverse events were observed in patients receiving this treatment.
The researchers also analyzed two forms of the tau protein in the central nervous system (CNS)—a reliable indicator of disease—during the study period and found a more than 50% reduction in total tau levels and tau concentrations. phosphate in the CNS after 24 weeks in the two treatment groups that received the highest dose of the drug.
Dr Mummery said: “We will need more research to understand the extent to which the drug can slow the progression of physical symptoms of the disease and to test the drug in larger groups of older people and in more diverse populations. But the results are an important step forward in showing that we can successfully target tau with a gene-silencing drug to delay, or possibly even reverse, Alzheimer’s and other diseases caused by tau accumulation in the future.” .
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