Health & Medicine, UK (Commonwealth Union) – The University College London (UCL) and the University College London Hospitals (UCLH) have discovered in a world 1st trial new genetic therapy for Alzheimer’s disease (AD) capable of safely and successfully reducing the levels of tau protein that can lead to the disease.
Tau proteins are a type of protein found in the brain and nervous system. They are primarily responsible for stabilizing the structure of microtubules, which are critical components of the cellular transport system in neurons.
In healthy neurons, tau proteins help to maintain the structure and function of microtubules, which are involved in transporting important molecules within the cell. However, in certain neurodegenerative diseases such as AD, tau proteins can become abnormally phosphorylated and form tangles, leading to disruption of the microtubule structure and subsequent neuronal dysfunction.
The study was, led by consultant neurologist Dr Catherine Mummery (UCL Queen Square Institute of Neurology & the National Hospital for Neurology and Neurosurgery), which was the 1st time the ‘gene silencing’ was considered for dementia and AD.
The trial involved the application of a drug known as BIIB080 (/IONIS-MAPTRx), which is an antisense oligonucleaotide, that halts RNA forming a protein, silencing the gene coding for the tau protein referred to as the microtubule-associated protein tau (MAPT) gene. This stops the gene getting translated into the protein in a doseable as well as a reversible way. It further brings down the formation of that protein and changes the course of disease, according to researchers.
More trials are required in wider groups of patients to find out if this brings about a clinical advantage, however the phase 1 findings appearing in Nature Medicine, that had results from 46 patients have been the 1st sign that this technique leads to a biological effect.
Treatments that target tau are unavailable right now. The drugs aducanumab and lecanemab – that gained approval recently for the application in certain situations by the FDA targets a different disease mechanism in AD, the amyloid plaque buildup.
The phase 1 trial explored the safety of BIIB080, its activities in the body, and how successfully the MAPT gene is targeted. The UCL Dementia Research Centre, played a role with the backing of the NIHR UCLH Biomedical Research Centre, with support from the NIHR UCLH Biomedical Research Centre, occurring at the Leonard Wolfson Experimental Neurology Centre at NHNN.
46 patients, averaging 66 years old, got recruited for the trial occurring from 2017 to 2020. The trial evaluated 3 drug doses, administered by intrathecal injection and was contrasted with the placebo.
The findings demonstrated that the drug had good toleration, with all patients participating in the entire treatment period and more than 90 percent finishing the post-treatment period.
The patients that took part in the treatment as well as the placebo groups had shown either mild or moderate side effects. The most frequent side effect was a headache following the injection of the drug. But, no major adverse events were observed for patients administered the drug, according to researchers.
The study team further explored 2 forms of the tau protein within the central nervous system (CNS) which is a suitable indicator of AD in the duration of the research.
They discovered over 50 percent less levels of total tau as well as phosphor tau concentration in the CNS following 24 weeks in the 2 treatment groups that were provided the largest dose of the drug.
“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,” explained Dr Mummery.
“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.”
