Key Points
- The cheap HIV pill maraviroc dampens the accumulation of harmful tau protein aggregates — a hallmark of neurodegenerative diseases like Alzheimer’s — in a neurodegenerative mouse model.
- Maraviroc treatments improve cognition in the same neurodegeneration model.
- Maraviroc inhibits a neuronal membrane receptor, CCR5, to improve neuronal capacity to clean up cell waste (a process called autophagy).
Neurodegenerative diseases have been estimated to affect 1% to 2% of the population aged 65 years and older, making these devastating conditions relatively common for older people. A neurological hallmark for neurodegeneration is the accumulation of tau protein aggregates, dysfunctional proteins which conglomerate among neurons, in the brain. To counter the cognitive decline tied to neurodegenerative diseases, researchers continuously seek molecules and compounds to abet neurodegeneration.
Published in Neuron, Rubinsztein and colleagues from the UK Dementia Research Institute in England show that maraviroc reduces tau protein aggregates in a mouse model for neurodegeneration. In doing so, maraviroc also improves cognition in the mouse model. Maraviroc inhibits a neuronal membrane receptor, CCR5, that receives signals from nervous system immune cells called microglia and reduces autophagy to drive tau protein aggregate accumulation. Since maraviroc has already received FDA approval, the findings offer hope of utilizing this cheap drug to counter neurodegenerative diseases like Alzheimer’s disease.
“We’ve not just found a new mechanism of how microglia hasten neurodegeneration, we’ve also shown this can be interrupted, potentially even with an existing, safe treatment,” said Professor Rubinsztein, the paper’s principal investigator, in a press release.
Maraviroc Reduces Brain Tau Protein Aggregates and Improves Cognition
To find whether maraviroc has any effects on tau aggregates, Rubinsztein and colleagues treated neurodegenerative mice having excessive tau with maraviroc for four weeks. The researchers found that maraviroc cut tau aggregate accumulation by about a third. These findings suggest that maraviroc can be used to diminish tau protein aggregates.
Since neurodegenerative diseases that include excessive tau are accompanied by cognitive deficits, the British researchers measured maraviroc’s effects on cognition. Four weeks of maraviroc treatment improved cognition for the mice with neurodegeneration as measured with a novel object recognition test. Mice prefer to examine novel objects, so the test involves both novel and familiar objects. The amount of time spent around novel objects tests memory, because more time around familiar objects portrays a lack of memory for those objects. It was found that maraviroc increases novel object preference, suggesting that maraviroc restores cognitive function and memory.
To better understand the cellular mechanism by which maraviroc reduces tau buildup and improves cognition, Rubinsztein and colleagues measured a brain protein marker for autophagy — LC3-II. Although lower levels of this marker in the brian suggested reduced autophagy in the neurodegeneration mouse model, treating the mice with maraviroc restored their autophagy. These results suggest that maraviroc improves autophagy so that neurons can clear their cell waste, thereby reducing dysfunctional protein aggregates.
Repurposing the HIV Pill Maraviroc Against Neurodegeneration
The study shows that maraviroc’s mechanism of inhibiting the CCR5 neuronal membrane receptor improves autophagy. The autophagic cell waste cleanup could be a means by which neurons remove dysfunctional tau protein aggregates. Interestingly, maraviroc treatment is also associated with improved cognition. By reducing tau protein accumulation, the brain may function better, which could explain why maraviroc improves cognition in the face of neurodegeneration.
Maraviroc is currently used to prevent AIDS. In the future, perhaps maraviroc will be used for neurodegenerative diseases like Alzheimer’s disease in humans. The first step is to find whether its effects against neurodegeneration in mice translate to humans. For this purpose, researchers may develop clinical trials to test maraviroc, which costs $8.74 per pill.
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