A new approach to slowing the ravages of Alzheimer's disease has shown promise in early studies on mice and monkeys, and is "worth investigating" in humans, US scientists said Wednesday.
The method involves injecting a synthetic compound in the brain that reduces the amount of a protein called tau which can accumulate, damage cells and lead to failures of memory.
"We've shown that this molecule lowers levels of the tau protein, preventing and, in some cases, reversing the neurological damage," said senior author Timothy Miller, professor of neurology at Washington University School of Medicine.
The molecule, known as an antisense oligonucleotide, works by targeting genetic instructions for tau before it is ever made, said the report in the journal Science Translational Medicine.
"This compound is the first that has been shown to reverse tau-related damage to the brain that also has the potential to be used as a therapeutic in people," added Miller.
Much more work is needed to test whether it is safe in humans, and whether it works the same in people as in animals.
"But everything we've seen so far says that this is worth investigating as a potential treatment for people," said Miller.
Researchers are cautious because mouse models of Alzheimer's are not exactly the same as the disease that affects humans.
Past research has failed to find an effective treatment for Alzheimer's, the most common form of dementia.
According to the World Health Organization, 47.5 million people have dementia worldwide.
What it did
In mice, the treatment "significantly reduced" tau compared to mice given a placebo, said the report.
The compound appeared not only to stop but reverse some of the tau buildup. In 12-month-old mice, levels of total tau and tau tangles in the brains were lower than in untreated nine-month-old mice.
"The treated mice lived an average of 36 days longer than untreated mice, and they were better at building nests, which reflects a combination of social behavior, cognitive performance and motor capabilities," said the report.
In monkeys, researchers injected two doses of placebo or oligonucleotide, one week apart, directly into the cerebrospinal fluid that surrounds the spinal cord and brain.
Two weeks later, tau protein in the monkeys' brains and cerebrospinal fluid was reduced.
Other treatments using oligonucleotide have been approved by the US Food and Drug Administration for Duchenne's muscular dystrophy and spinal muscular atrophy.
California-based Ionis Pharmaceuticals discovered the oligonucleotide for spinal muscular atrophy, and partnered with Miller to develop the oligonucleotide treatment for reducing tau.
Human trials are already under way, using oligonucleotides against Huntington's disease and amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease.
Gordon Wilcock, Emeritus professor of geratology at the University of Oxford, described the tau work as "important."
"However, results in animal models are a long way from treating humans," said Wilcock, who was not involved in the study.
"Not only will the treatment's safety have to be established before clinical trials can take place, but also an alternative and more practical way of delivering this treatment to the brain is needed."