A new genetic therapy for Alzheimer’s disease is safe and successfully lowered levels of the harmful tau protein known to cause the disease, a new study suggests.
Researchers say the findings are a “significant” step forward in demonstrating it may be possible to target the protein to slow, or potentially even reverse, the disease.
The world first trial at University College London Hospitals NHS Foundation Trust and UCL represents the first time a gene silencing approach has been taken in dementia and in Alzheimer’s.
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— Dr Catherine Mummery
The findings indicate scientists can alter the amount of tau – one of the proteins that cause Alzheimer’s – by silencing the messages from DNA that make the abnormal protein within each cell, with a drug called BIIB080 (MAPTRx).
According to the phase 1b trial results, the drug prevents the gene from being translated into the protein in a doseable, reversible way.
This can then lower the production of that protein and alter the course of disease, the research suggests.
Consultant neurologist Dr Catherine Mummery at the National Hospital for Neurology and Neurosurgery, 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.”
Further trials will be needed in larger groups of patients to determine whether the findings lead to clinical benefit.
But the results published in Nature Medicine are the first indication that this method has a biological effect.
There are currently no treatments targeting tau.
The trial looked at the safety of MAPTRx, what it does in the body and how well it targets the gene.
It involved the UCL Dementia Research Centre, was supported by the NIHR UCLH Biomedical Research Centre, and took place at the NIHR UCLH Clinical Research Facility at Queen Square.
Forty-six 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 an injection into the nervous system via the spinal canal, compared with placebo.
According to the study, the drug was well tolerated, with all patients completing the treatment period and more than 90% completing the post-treatment period.
Patients in both the treatment and placebo groups experienced either mild or moderate side effects.
The most common side effect was headache after the injection, but no serious adverse events were seen in patients given the drug.
While there is a long way to go in larger trials to determine whether this drug will help people living with dementia, the data are very promising— Tara Spires-Jones, University of Edinburgh
Researchers also looked at levels of two forms of the tau protein in the central nervous system (CNS) – a reliable indicator of disease – over the duration of the study.
They found a greater than 50% reduction in levels of total tau and phosphor tau concentration in the CNS after 24 weeks in the two treatment groups which received the highest dose of the drug.
Tara Spires-Jones, professor of neurodegeneration and deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh, said: “Excitingly, in this small study there was also very promising reduction of tau in the cerebrospinal fluid after treatment.
“While there is a long way to go in larger trials to determine whether this drug will help people living with dementia, the data are very promising.
“This type of treatment targeting tau has the potential to slow or even hopefully stop Alzheimer’s disease progression, so I very much look forward to seeing results from the next stages of testing.”
Dr Liz Coulthard, associate professor in dementia neurology, at the University of Bristol, said: “As this is a phase 1 study, all it tells us is that the drug is good enough to take to full trials, ie the drug blocks the production of harmful protein without causing obvious dangerous side effects.
“Bigger trials are needed to test whether this effect actually helps individual patients. These trials are under way.
“This treatment works on a different protein to lecanemab, the drug recently licensed in the US and under regulatory review here.
“One major drawback to this treatment is that it needs to be given by injection into the lumbar spine ie by lumbar puncture.”
