Newswise —
A pioneering experiment at UCL and UCLH has discovered a novel genetic treatment for Alzheimer's disease that can safely and effectively reduce the levels of the detrimental tau protein, which is recognized as the cause of the disease.
The study, overseen by Dr. Catherine Mummery, a consulting neurologist at the UCL Queen Square Institute of Neurology & the National Hospital for Neurology and Neurosurgery, marks the initial instance where a technique known as "gene silencing" has been utilized for dementia and Alzheimer's disease.
The strategy employs a medication named BIIB080 (/IONIS-MAPTRx), which is an antisense oligonucleotide used to prevent RNA from generating a protein, to "silence" the microtubule-associated protein tau (MAPT) gene, which encodes the tau protein. This inhibits the translation of the gene into the protein in a measurable and reversible manner, leading to a reduction in protein production and a modification in the progression of the disease.
To establish whether this method translates into clinical advantages, additional studies will be necessary with larger patient cohorts. However, the outcomes of phase 1, which included 46 participants and were published in Nature Medicine, provide the first evidence that this technique produces a biological impact.
At present, there are no therapies that specifically target tau. The medications aducanumab and lecanemab, which were recently granted FDA approval for certain situations, aim to address a distinct mechanism of the disease in AD - the buildup of amyloid plaques*.
The phase 1 trial was conducted to examine the safety of BIIB080, its mechanism of action in the body, and its ability to specifically target the MAPT gene. The study was conducted at the Leonard Wolfson Experimental Neurology Centre at NHNN and involved the UCL Dementia Research Centre. The trial received support from the NIHR UCLH Biomedical Research Centre.
The trial, conducted from 2017 to 2020, enrolled 46 participants with an average age of 66. The study examined the effects of three different doses of the drug, which were administered through an intrathecal injection (an injection into the nervous system via the spinal canal), compared to a placebo.
The outcomes indicate that the drug was well-tolerated, as all participants completed the treatment period, and over 90% completed the post-treatment period.
Patients in both the treatment and placebo groups experienced mild or moderate side effects, with the most frequent being a headache following the administration of the drug. Nonetheless, no severe adverse effects were observed in patients who were administered the medication.
Throughout the study period, the research team also evaluated two forms of the tau protein in the central nervous system (CNS), which are reliable biomarkers of the disease.
The study observed a reduction of more than 50% in the concentrations of total tau and phospho-tau in the CNS after 24 weeks in the two treatment groups that received the highest dose of the drug.
Dr. Mummery stated, "Additional research will be necessary to determine the extent to which the medication can impede the progression of physical symptoms of the disease, evaluate the drug's effectiveness in larger and older patient cohorts and more diverse populations."
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