A genetic treatment that delivers a virus to a gene in the brain could be used treat early-stage Alzheimer's disease, says research published in the journal Proceedings of the National Academy of Sciences.

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In Alzheimer's, amyloid plaques build up in the brain.

Alzheimer's disease is the most common kind of dementia. It affects over 40 million people worldwide, bringing memory loss, confusion, and personality or mood changes. There is currently no cure.

In 2013, the Centers for Disease Control and Prevention (CDC) estimated that up to 5 million people were living with Alzheimer's in the United States. In 2014, 93,541 deaths were attributed to the disease, making it the sixth main cause of death in the U.S.

Scientists from Imperial College London in the United Kingdom have now used a modified virus to deliver a gene, known as PGC1-alpha, to the brain cells of mice. They found that it reduced the development of Alzheimer's.

The virus is called a lentivirus vector, and it is commonly used in gene therapy.

On the basis of previous lab research, the team predicted that it might stop a protein called amyloid-beta peptide from forming in cells.

Amyloid plaques are sticky clumps of protein that occur in the brains of people with Alzheimer's disease. They are believed to be responsible for the death of brain cells. Amyloid-beta peptide is the main component of these plaques.

Prof. Nicholas Mazarakis, co-author of the study, explains how scientists can turn the way the lentivirus infects cells to their advantage; it involves producing a modified version of the virus and using it to deliver genes into specific cells.

Scientists are already using the technique to research treatments for arthritis, cancer, and other conditions. In clinical trials, the current team has used it successfully to deliver genes into the brains of people with Parkinson's disease.

The cortex and the hippocampus

In this latest study, the researchers injected the virus into two areas of the brains of mice: the cortex and the nearby hippocampus.

Alzheimer's is believed to start in the cortex, and then gradually spread to the hippocampus. The first damage may occur 10-20 years before the disease becomes outwardly visible.

The cortex is associated with long-term memory, reasoning, thinking, and mood. Damage may result in depression and difficulty figuring out how to do familiar tasks.

The hippocampus is instrumental in learning, in converting short-term memories into long-term memories, and in orientation. Damage to the hippocampus can cause a person to forget recent events, such as what they did this morning. It is also the reason why people with Alzheimer's get lost on familiar routes - for example, being unable to find the way home.

Slower development of amyloid plaques

The mice that received the treatment had early-stage Alzheimer's. They had not yet developed amyloid plaques. They were injected with the adapted virus containing the PGC1-alpha gene.

Four months after the injections, tests showed that the mice that had received the gene had very few amyloid plaques, a better memory, and no loss of brain cells in the hippocampus. Those that had not been treated had multiple plaques in their brain.

To test for memory, the team replaced a familiar object in the mouse cages with a new item. Those with a healthy memory explored the new object for longer. The treated mice performed as well as healthy mice.

The treated mice also had a lower number of glial cells. In Alzheimer's disease, glial cells are thought to cause additional cell damage by releasing toxic inflammatory substances.

"Although these findings are very early, they suggest this gene therapy may have potential therapeutic use for patients. There are many hurdles to overcome, and at the moment the only way to deliver the gene is via an injection directly into the brain. However, this proof-of-concept study shows this approach warrants further investigation."

Senior author Dr. Magdalena Sastre

The authors hope that the findings could open a new pathway to future therapies, either to prevent the disease or to stop it in the early stages. They hope to start looking at how to apply the treatment in humans, although they point out that it will be years before it can be used in a clinical setting.

They believe this treatment would be best used in the early stages of Alzheimer's, when symptoms first appear.

Dr. David Reynolds, chief scientific officer at Alzheimer's Research UK, calls the results "a promising step on the road towards developing treatments for this devastating condition."

PGC1-alpha plays a role in the regulation of sugar and fat metabolism in the body. Other studies have suggested that physical exercise and resveratrol - a compound that features in red wine - may increase levels of PGC1-alpha.

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