A prospective treatment that ‘silences genes’ may slow the progression of Alzheimer’s and may have the potential to reverse the disease, according to a small study by researchers at University College London.
In the world-first trial, the researchers tested an antisense oligonucleotide drug, used to stop RNA from producing proteins, to ‘silence’ the gene coding for the tau protein in the brain which is known to cause Alzheimer’s.
The drug currently known as BIIB080 (/IONIS-MAPTRx) prevented the gene from being translated into the protein in a doseable way and could be used to lower protein levels in the brain.
The findings are published this week in Nature Medicine and highlight the potential for ‘gene silencing’ to reverse the onset of Alzheimer’s Disease (AD).
Almost one million people in the UK have dementia, and there are currently no treatments which target the tau protein involved in AD. The drugs aducanumab and lecanemab, recently approved for use in some situations by the FDA, target a separate disease mechanism which prevents the accumulation of amyloid plaques.
The researchers recruited 46 patients to phase 1 of the trial, which took place at the National Hospital for Neurology and Neurosurgery, part of the University College London Hospitals NHS Foundation Trust between 2017 and 2020. Participants were all between 50 and 74 years old and had mild AD, defined by a Clinical Dementia Rating (CDR).
The trial analysed the effect of three drug doses injected into the nervous system via the spinal canal, compared to a placebo. The study examined two forms of the tau protein in the central nervous system.
After 24 weeks of treatment, the researchers found a greater than 50% reduction of total tau levels and the concentration of phosphor tau in the central nervous system for participants on the highest drug dose.
The trialled drug was well tolerated, with all participants completing the treatment during the trial. Both the treatment and the placebo group reported mild or moderate side effects, the most common of which was a headache after injection of the drug.
The researchers state that further trials involving more participants will be needed but are encouraged that the first trial has shown a biological effect.
Dr Catherine Mummery, a consultant neurologist at UCL who led the trial, said: ‘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.’
‘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.’