Gene therapy halts Alzheimer's disease in mice: study

British researchers said Monday they have prevented the development of Alzheimer's disease in mice by using a virus to deliver a specific gene into the brain, an advance that may lead to potential new treatments for the disease.

This gene, called PGC1-alpha, may prevent the formation of a protein called amyloid-beta peptide, which is the main component of amyloid plaques found in the brains of Alzheimer's patients, according to previous studies in lab cells by the same team.

The early-stage findings, by scientists from Imperial College London, were published in the U.S. journal Proceedings of the National Academy of Sciences.

"Although these findings are very early, they suggest this gene therapy may have potential therapeutic use for patients," Magdalena Sastre, senior author of the research from the Department of Medicine at Imperial, said in a statement.

"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."

The modified virus used in the experiments was called a lentivirus vector, and is commonly used in gene therapy.

In the new study, the team injected the virus, containing the gene PGC-1-alpha, into two brain areas linked to memory in mice susceptible to Alzheimer's disease.

The areas targeted were the hippocampus and the cortex, as these are the first regions to develop amyloid plaques in Alzheimer's disease.

The animals were treated at the early stages of Alzheimer's disease, when they still had not developed amyloid plaques.

After four months, the team found that mice who received the gene had very few amyloid plaques, compared with the untreated mice, who had multiple plaques in their brain.

Furthermore, the treated mice performed as well in memory tasks as healthy mice.

The team also discovered there was no loss of brain cells in the hippocampus of the mice who received the gene treatment. In addition to this, the treated mice had a reduction in the number of glial cells, which in Alzheimer's disease can release toxic inflammatory substances that cause further cell damage.

Sastre added that other studies from different institutions suggest physical exercise and the compound resveratrol, found in red wine, may increase levels of PGC-1-alpha protein.

However, resveratrol has only been found to have benefits as a pill, rather than in wine, as the alcohol counteracts any benefit, she said.

The team now hoped to explore translating their findings into human treatments.

"We are still years from using this in the clinic. However, in a disease that urgently needs new options for patients, this work provides hope for future therapies," said Sastre.

Tara Spires-Jones, interim director of the Center for Cognitive and Neural Systems at the University of Edinburgh, who was not involved in the study, said this study should be interpreted with caution as the results are based on very few mice in only one model of the disease.

"These results will need to be replicated in multiple models and many hurdles overcome to know whether this type of treatment will be useful for human patients," Spires-Jones added.

Worldwide 47.5 million people are affected by dementia, of which Alzheimer's is the most common form. The disease's symptoms include memory loss, confusion, and change in mood or personality. Endit