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. Healthy bodies are typically capable of clearing out diseases and pathogens in the brain with immune cells called microglia. 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. Specifically, the authors repurposed an HIV drug called maraviroc to do so. Maraviroc was approved by the FDA to treat the autoimmune disease in 2007.
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“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 the new study, the authors genetically engineered mice to develop specific forms of Huntington’s disease, which is caused by build-ups of misfolded proteins. 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. Once flipped, it can cause white blood cells to allow for the build of of more proteins.
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. That’s how the team turned to maraviroc, an HIV drug that inhibited the receptor, to fight neurodegenerative conditions in mice.
The study’s authors used the drug to treat mice with Huntington’s for 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. The mice were also shown to perform memory and object recognition tests better than untreated mice.
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. “During the development of this drug as a HIV treatment, there were a number of other candidates that failed along the way because they were not effective against HIV. 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. This time, it could be a drug being used to fight two of the most pernicious and life-affecting illnesses in human history.
