HIV drug is expected as a treatment for dementia

Two recent studies show that a well-known HIV drug shows promise in treating dementia.

In 2007, the United States and the European Union approved a drug called maraviroc (muh-RAV-a-roc) for the treatment of HIV.

Now, in an independent study, researchers from the University of Cambridge and the University of California, Los Angeles have shown the effectiveness of maraviroc in treating conditions that cause dementia and Huntington’s disease in mice.

In a new study by the University of Cambridge, scientists have discovered how the brain’s ability to clear harmful proteins is impaired in Huntington’s disease and other dementias, and how maraviroc might help this function. showed that they were able to recover and prevent the accumulation of toxic proteins. slow the progression of the disease.

A common feature of neurodegenerative diseases is the accumulation of clusters in the brain called aggregates containing misfolded proteins known as huntingtin and tau. These clumps cause brain cell breakdown and eventual death, leading to the development of dementia symptoms.

One method that mammals use to clear aggregates from the brain is called autophagy (awe-TOFF-o-gee), Latin for “self-eating.” In this process, neighboring cells “eat” unwanted substances, break them down, and excrete them. Neurodegenerative diseases impair autophagy and cause accumulation of toxic misfolded proteins.

In their study published in the journal neurona team from the Cambridge Institute of Medicine and the UK Institute for Dementia at the University of Cambridge, has identified the process responsible for autophagy failure in mouse models of dementia and Huntington’s disease and how maraviroc can help restore it. .

The mammalian brain and central nervous system have specialized immune cells called microglia that specialize in defending against unwanted toxic substances. In neurodegenerative diseases, microglia (mi-KROL-glee-uh) are still activated, but actually act in a way that impairs autophagy, the self-eating process that removes toxins.

Using mice, the researchers showed that in the presence of neurodegenerative disease, the same immune-boosting microglia release a series of molecules that activate cell-surface switches called CCR5. This switch abnormally impairs autophagy and the brain’s ability to remove harmful proteins.

These proteins start to aggregate and cause irreversible damage to the brain. To make matters worse, the same toxin creates a feedback loop that triggers a greater response from immune-boosting microglia, activating more CCR5 cells, further impairing autophagy and causing further accumulation of aggregates. It’s faster.

Lead author of the study, Professor David Rubinstein of the Cambridge Institute for Dementia Research, explained in a statement released with the study: This suggests, as we expected, that if we are to find effective treatments for diseases such as Huntington’s disease and dementia, we need to start treatment before symptoms begin to appear. I’m here. ”

The researchers used mice that were genetically modified to develop Huntington’s disease, a type of dementia characterized specifically by accumulation of tau protein.

When the researchers used mice bred to ‘knock out’ the work of CCR5 cells, these mice were protected from the accumulation of misfolded huntingtin and tau, showing that their brains were more affected than control mice. It has been found to lead to a reduction in toxic aggregates within the .

The CCR5 switch is not only exploited by neurodegenerative diseases, but is also used by HIV as a ‘gateway’ into cells.

This connection inspired the team to use maraviroc to treat Huntington’s disease mice. The researchers administered the drug for four weeks, starting at two months of age. At that time point, we found a significant reduction in the number of huntingtin aggregates compared to untreated mice. However, Huntington’s disease causes only mild symptoms in mice by 12 weeks without treatment, and it was too early to tell whether maraviroc affected symptoms in mice.

The same effect was also observed in the dementia control group. In these mice, maraviroc not only reduced the amount of tau aggregates compared to untreated mice, but also delayed brain cell loss. An object recognition test revealed that treated mice performed better than untreated mice, suggesting that the drug delayed memory loss.

“We are very excited about these findings because they not only reveal a new mechanism by which microglia promote neurodegeneration, but they also show that even existing safe treatments may be able to block neurodegeneration. “I’m excited about it,” said Professor Rubinstein. ”

A similar study on the other side of the globe came to the same conclusion. Maraviroc is effective for amnesia in mice.

Last May, UCLA neuroscientist Arcino Silva also studied the effects of the CCR5 switch on memory, specifically how memory connections are formed. Silva told NPR that the brain can form new memories as it ages, but it’s difficult to connect them.

“You learn about something,” Silva explained. “But I can’t remember where I heard it. I can’t remember who told you about it. As we get middle-aged and older, these incidents happen more and more often.”

CCR5 was found to interfere with memory-binding processes, such as the integration of names and faces, in the same way that it affects the accumulation of toxic proteins in the brain.

“The molecule turns off the memory mechanism, so you can’t link memories after that,” Silva says.

So Silva’s team, like the Cambridge research group, tried maraviroc. Just as maraviroc restores autophagic function and removes toxic proteins, it helped restore memory connections.

Silva’s research Naturefound that levels of CCR5 spiked after stroke in a previous study with Thomas Carmichael, director of neurology at UCLA. Carmichael is now applying Silva’s work with Maraviroc to stroke patients.

“It can affect Alzheimer’s disease, stroke, Parkinson’s disease, and spinal cord injuries,” says Carmichael.

“Maraviroc by itself may not be a silver bullet, but it shows potential,” said Rubinstein of the Cambridge study. “During the development of this drug as a treatment for HIV, there were also a number of other drug candidates that failed along the way because they were ineffective against HIV. Of these, he said, one was to prevent neurodegenerative disease in humans. It may prove to work effectively for

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