Dementia comes in different forms but a common feature is the build-up in the brain of clusters of abnormal proteins which leads to the eventual death of brain cells.
One of the ways our body rids itself of these toxic proteins is through autophagy, or ‘self-eating’, where cells eat the toxic material, break it down and discard it.
In diseases such as dementia, autophagy doesn’t work, meaning the brain can’t get rid of the toxic proteins, so they accumulate and destroy brain cells and connections.
But Cambridge University scientists have shown how a repurposed HIV drug can restore the brain’s autophagy capability, helping prevent this build-up of destructive proteins and thereby slow progression of the disease.
The brain and central nervous system have their own special immune cells called microglia, which should protect the brain against unwanted and toxic materials.
In neurodegenerative diseases, microglia release chemicals which activate a switch called CCR5 that stops the brain ridding itself of the toxic proteins.
Professor David Rubinsztein from Cambridge University, the study’s senior author, said: “The microglia begin releasing these chemicals long before any physical signs of the disease are apparent.
“This suggests – much as we expected – that if we’re going to find effective treatments for diseases such as Huntington’s and dementia, they need to begin before an individual begins showing symptoms.”
When the action of CCR5 was knocked out, there were fewer of the toxic proteins found in the brain.
The CCR5 switch is also used by HIV as a ‘doorway’ into our cells.
In 2007, the US and European Union approved a drug known as Maraviroc, which inhibits CCR5, as a treatment for HIV.
The Cambridge team have tried using Maraviroc to treat dementia in mice and not only did the drug reduce the amount of proteins, but it also slowed down the loss of brain cells, suggesting that the drug might even slow down memory loss.
Prof Rubinsztein says: “Maraviroc may not itself turn out to be the magic bullet, but it shows a possible way forward.
“During the development of this drug as an HIV treatment there were a number of other candidates that failed along the way because they were not effective against it.
“We may find that one of these works effectively in humans to prevent neurodegenerative diseases.”
That would be a huge step forward.
