Neurodegenerative conditions like dementia impact tens of millions of people worldwide every year. While there’s still a lot we don’t understand about diseases like Alzheimer’s, Parkinson’s, and Huntington’s, we do know that the issues largely seem to stem from misfolded proteins–or, rather, our body’s inability to clear them out of our brains.
As they build up, these toxic proteins can kill brain cells and trigger diseases like Alzheimer’s. Microglia, a type of immune cell in healthy bodies is capable to remove pathogens and diseases from the brain. However, neurodegenerative diseases actually cause the immune cells to harm healthy cells–and encourage the build up of proteins.
Targeting these proteins has long been a goal for scientists developing treatments for dementia. That’s why a team of researchers from the University of Cambridge in the U.K. published a study Wednesday in the journal Neuron that detailed a new approach clearing out clusters of the proteins in mice. The authors used a drug known as maraviroc, which was originally developed to treat HIV. Maraviroc was approved by the FDA to treat the autoimmune disease in 2007.
“We’re very excited about these findings because we’ve not just found a new mechanism of how our microglia hasten neurodegeneration, we’ve also shown this can be interrupted, potentially even with an existing, safe treatment,” senior author David Rubinsztein, a dementia researcher at Cambridge, said in a statement.
For this new study, authors genetically modified mice to develop Huntington’s Disease, caused by a buildup of misfolded protein. Over the course of experimental trials, they found that microglia actually released molecules that impaired the clearing of proteins by impacting a receptor called CCR5 on white blood cells that essentially acts like a switch. It can be flipped to cause the white blood cells allow more protein build up.
This process actually can cause a feedback loop in which CCR5 led to even more build ups of proteins, which led to more CCR5 leading to more proteins, which led to… you get the picture.
However, they found that if they bred mice that had cells with inhibited CCR5 receptors, then they were protected against Huntington’s disease and proteins would build up less in these animal models. Coincidentally, CCR5 is also involved in how HIV targets our cells. Maraviroc is an HIV drug which inhibits the receptor. This was how the team decided to use it to treat neurodegenerative diseases in mice.
The study authors treated mice for Huntington’s disease with the drug over a period of four weeks. By the end of the trial, they discovered that there were significantly less protein build ups when compared to mice who weren’t treated with the drug. They also showed that the mice performed better on memory tests and in object recognition than mice who were not treated.
It should be noted though that Huntington’s is fairly mild in mice even without treatment. More research is needed to definitely show its efficacy in treating the disease in humans.
“Maraviroc may not itself turn out to be the magic bullet, but it shows a possible way forward,” Rubinsztein said. In the process of developing this drug for HIV treatment, a few other candidates failed because they weren’t effective. We may find that one of these works effectively in humans to prevent neurodegenerative diseases.”
It’s always interesting to see a drug intended for one purpose potentially find new life treating something else. It could happen that a drug is used to combat two of humanity’s most deadly and pernicious diseases.
The article An HIV drug shows signs of guarding against dementia first appeared on The Daily Beast .
