Dementia: How an HIV drug may protect against brain protein build-up

  • A repurposed HIV drug may help the brain clear toxic proteins and slow the progression of dementia.
  • Researchers report that mice given the medication improved on object recognition tests.
  • There are different types of dementia, but researchers say it’s possible they all involve inflammation

When someone has dementia, including Huntington’s disease, the brain’s ability to clear toxic proteins is impaired.

In a study published today in the journal Neuron, researchers looked at using maraviroc (Selzentry), an antiretroviral treatment approved for HIV, and reported it could help restore this function in mice, allowing them to perform better at object recognition tests and slowing the loss of brain cells.

The researchers from the Cambridge Institute for Medical Research and the UK Dementia Research Institute at the University of Cambridge in England identified that autophagy did not correctly work in mice with dementia, including Huntington’s disease.

Autophagy, meaning self-eating, is the process of cells eating unwanted material, breaking it down, and discarding it.

Toxic proteins in the brain

Some forms of neurodegenerative diseases result in a buildup of toxic proteins in the brain. These include misfolded huntingtin proteins in Huntington’s disease and tau tangles in Alzheimer’s disease.

This can lead to the degradation and death of brain cells.

As toxic protein buildup continues and causes irreversible brain damage, their activity increases and the buildup rate increases.

Specific immune cells in the brain, called microglia, typically help to protect against the toxic buildup. However, in many neurodegenerative diseases, these cells are activated and instead can impair the process of autophagy.

Details from the dementia study

For the study, the scientists bred some of the mice to stop the impairment and allow autophagy to occur. This protected these mice from a buildup of toxic proteins.

Then, the research team administered maraviroc to mice with Huntington’s disease for four weeks, starting when the mice were 2 months old.

They reported there was a significant reduction in the number of huntington protein aggregates. However, because the disease only manifests mild symptoms by 12 weeks, it was too soon to tell if the drug would have any impact.

The scientists also used this treatment in mice with dementia, reducing the number of tau aggregates in the brain. The mice received an object recognition test and the ones treated performed better, suggesting the treatment slowed memory loss.

“This is very exciting and novel research. However, it is still very early in the process,” said Dr. Marc Gordon, the chief of neurology at Zucker Hillside Hospital in New York.

“Typically, from this point, if all goes well, it could take 12 to 15 years to get to a new drug. However, since the researchers used an existing drug, it could be as soon as five to eight years,” he told Medical News Today.

The Food and Drug Administration (FDA) approved maraviroc for the treatment of HIV. Repurposing the drug means that safety trials have already occurred. This can significantly reduce the time and expense needed to develop a new drug.

Searching for answers

Dementia refers to the loss of cognitive function, according to the National Institutes of Health.

Alzheimer’s disease is the most common type of the disease. Other types include:

  • Creutzfeldt-Jakob disease
  • Dementia with Lewy Bodies
  • Frontotemporal dementia
  • Huntington’s disease
  • Parkinson’s disease dementia
  • vascular dementia
  • Korsakoff syndrome

“Finding new ways of looking at dementia, such as Huntington’s, is helpful,” said Dr. David Merrill, an adult and geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in California.

“Looking at potential other causes of dementia could help us find treatments,” he told Medical News Today. “Right now, around 99 percent of drug trials for dementia have failed and there are no treatments, so new medications are needed.”

Over the past several years, scientists have linked inflammation with dementia.

A study completed in 2020 at the University of Cambridge reported that neuroinflammation was found across three different types of frontotemporal dementia. Neuroinflammation has also been linked to other neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.

This implies that it plays a role in many types of dementia.

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