Alzheimer’s reversed in mice under breakthrough treatment
LOS ANGELES: Alzheimer’s disease has been reversed in mice in a breakthrough that offers hope that the disease may one day be curable.
Spanish and Chinese researchers have found a way to restore the function of the blood-brain barrier, so it can clear out the sticky amyloid beta plaques that stop brain cells from communicating.
The blood-brain barrier is a “gatekeeper” that surrounds the brain, controls what enters and exits, and keeps out toxic substances, while allowing harmful substances inside to be cleared out.
In Alzheimer’s patients, these gatekeeping systems become clogged and inefficient, so researchers created nanoparticles which “remind” the barrier how to work properly.
Nanoparticles are injected into the bloodstream, where they travel to the barrier, attach to it and stimulate natural mechanisms, so that the brain can access nutrients and clear out waste, restoring healthy brain function.
Researchers tested the therapy in mice genetically programmed to produce large amounts of amyloid beta, which leads to significant cognitive decline, mimicking Alzheimer’s.
“Only one hour after the injection, we observed a reduction of 50-60 per cent in amyloid beta amount inside the brain,” said Junyang Chen – first co-author of the study, researcher at the West China Hospital of Sichuan University and PhD student at University College London (UCL).
Researchers then conducted experiments to analyse the behaviour of the animals and measure their memory decline over several months.
In one of the experiments, they treated a 12-month-old mouse – equivalent to a 60-year-old human – with nanoparticles and analysed its behaviour after six months. The animal’s behaviour became the same as a healthy mouse.
The treatment mimics a protein called LRP1 which recognises amyloid beta and attaches to it, ferrying it across the blood-brain barrier and unblocking clogged areas.
Once the vasculature is able to function again, it continues clearing amyloid beta and other harmful molecules, allowing the whole system to recover its balance.
The team now wants to conduct larger preclinical studies, before moving to early-stage trials in humans.
Prof Giuseppe Battaglia, of the Catalan Institution for Research and Advanced Studies (ICREA), who led the study said: “The progress so far is very encouraging; restoring the brain’s barrier could open a new path for treating not only Alzheimer’s but also other neurological diseases.
“Developing a new therapy takes time, but if the next studies confirm our results and we raise the necessary funds, the first clinical trials could begin within the next few years.
“We are optimistic that the benefits we’ve seen – improved blood flow, reduced brain inflammation, and recovery of the barrier – will translate to humans.
“The blood-brain barrier plays a similar role in all of us, so helping it heal could make a real difference in how we fight Alzheimer’s and other forms of dementia.”
There are estimated to be 944,000 people with dementia in Britain, with the majority suffering from Alzheimer’s.
The number is expected to increase to more than one million by 2030, with one in three people born in the UK this year expected to develop dementia in their lifetime.
The condition costs the country £34.7bn annually and is now the leading cause of death, but there are no licensed drugs for the condition.
The research was published in the journal Signal Transduction and Targeted Therapy