Gene therapy could ward off Alzheimer's disease altogether


No currently available treatment can halt or delay the progression of Alzheimer’s disease, but Imperial College London researchers found that gene therapy may be able to prevent its onset altogether, at least in mice.

The team has previously that found the gene PGC-1-alpha may prevent the formation of amyloid beta, the protein that accumulates in the brains of people who have Alzheimer’s. In a study published in the Proceedings of the National Academy of Sciences, the scientists delivered this gene to the brains of mice using a modified virus, according to a statement. PGC-1-alpha codes for a protein of the same name that plays a part in the body’s metabolic function, including regulating sugar.

The virus in question, a lentivirus vector, is frequently used in gene therapy. The team injected the lentivirus containing the PGC-1-alpha gene into the hippocampus and the cortex in mice susceptible to the neurodegenerative disease, according to the statement. They chose these regions because they are the first to develop amyloid plaques in people with Alzheimer’s. Damage to the hippocampus affects short-term memory, while damage to the cortex affects long-term memory, reasoning, thinking and mood.

They injected the mice before they developed amyloid plaques. Four months later, they observed the mice that had undergone gene therapy had few amyloid plaques, while untreated mice had developed several plaques, according to the statement. The researchers also found that the treated mice showed no loss of brain cells in the hippocampus.

In addition to inspecting the mice’s brains for amyloid plaques, the scientists also assessed their performance on memory tasks. The treated mice did as well as healthy mice on these challenges, which included replacing a familiar object in a mouse’s cage with a new object.

About 5 million people are estimated to have Alzheimer’s in the U.S., while about 520,000 people in the U.K. are affected by the disease. Because there is no cure, current therapies focus on controlling symptoms. While the gene therapy is still a long way from the clinic, the team believes gene therapy would be most effective in early stages of the disease.

"Although these findings are very early they suggest this gene therapy may have potential therapeutic use for patients,” said Magdalena Sastre, senior author of the study and a senior lecturer in ICL’s department of medicine, in the 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."