by A new gene therapy for Alzheimer’s is safe and has successfully lowered levels of the harmful tau protein known to cause the disease, a new study suggests.
The researchers say the findings are a “significant” step in showing it may be possible to target the protein to slow, or potentially even reverse, the disease.
The world’s first study at University College London Hospitals NHS Foundation Trust and UCL represents the first time a gene silencing approach has been adopted in dementia and Alzheimer’s.
The findings indicate that scientists can alter the amount of tau — one of the proteins that cause Alzheimer’s — by silencing the DNA messages that produce the abnormal protein inside each cell, with a drug called BIIB080 (MAPTRx).
According to the results of the phase 1b trial, the drug prevents the gene from being translated into the protein in a measurable and reversible way.
This can then reduce the production of that protein and alter the course of the disease, the research suggests.
Dr Catherine Mummery, consultant neurologist at the National Hospital for Neurology and Neurosurgery who led the study, said: ‘We will need more research to understand to what extent the drug can slow the progression of the physical symptoms of the disease and assess the drug in older patients and larger groups of people and in more diverse populations.
“But the findings are a significant step forward in showing that we can successfully target tau with a gene silencing drug to slow — or perhaps even reverse — Alzheimer’s disease and other diseases caused by tau buildup in the future.”
Further studies in larger patient groups will be needed to determine whether the findings lead to clinical benefit.
But the findings published in Nature Medicine are the first indication that this method has a biological effect.
There are currently no treatments targeting tau.
The study looked at the safety of MAPTRx, what it does in the body and how well it affects the gene.
It involved UCL’s Dementia Research Centre, was supported by the NIHR’s UCLH Biomedical Research Centre, and took place at the NIHR’s UCLH Clinical Research Facility in Queen Square.
Forty-six patients with a mean age of 66 were enrolled in the study which ran from 2017 to 2020.
The study looked at three doses of the drug, given as an injection into the nervous system through the spinal canal, compared with placebo.
According to the study, the drug was well tolerated, with all patients completing the treatment period and over 90% completing the post-treatment period.
Patients in both the treatment and placebo groups experienced mild or moderate side effects.
The most common side effect was headache after the injection, but no serious adverse events were observed in patients receiving the drug.
The researchers also looked at levels of two forms of the protein tau in the central nervous system (CNS), a reliable indicator of the disease, throughout the duration of the study.
They found a greater than 50% reduction in total tau and tau phosphorus concentration levels in the central nervous system after 24 weeks in the two treatment groups that received the higher dose of the drug.
Tara Spiers-Jones, professor of neurodegeneration and deputy director of the Center for Discovery Brain Sciences at the University of Edinburgh, said: “Excitingly, there was also a very promising reduction in cerebrospinal fluid tau following treatment in this small study.
“While there is still a long way to go in larger studies to determine whether this drug will help people living with dementia, the data is very promising.
“This type of tau-targeted treatment has the potential to slow or even hopefully halt the progression of Alzheimer’s disease, so I look forward to seeing the results of the next phases of testing.”
Dr Liz Coulthard, associate professor of neurology of dementia, 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 be tested. to full evidence, i.e. the drug blocks the production of harmful proteins without causing obvious dangerous side effects.
“Larger studies are needed to see if this effect actually helps individual patients. These trials are ongoing.
“This treatment works on a different protein than lecanemab, the drug recently licensed in the US and under regulatory review here.
“One of the major disadvantages of this treatment is that it must be given by injection into the lumbar spine, which is a lumbar puncture.”
