Gene Therapy For Alzheimer’s Disease

Delivery of a gene called PGC1 – alpha may prevent amyloid beta plaque formation in Alzheimer’s disease

Many believe that the peptide amyloid beta and its associated plaques are behind Alzheimer’s disease – causing neuron death and disrupting brain function. PGC1-alpha may be a solution, according to previous research at Imperial College London. 

“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”

What is PGC1-alpha?

Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha) plays a central role in cellular metabolism and stimulates mitochondrial biogenesis and remodeling of muscle tissue among other functions. Previous research has also indicated that both exercise and resveratrol can stimulate PGC1-alpha expression. 

Lentiviral gene therapy

In a new study a research team injected a lentiviral vector containing the PGC1-alpha gene into the hippocampus and cortex in mice with particular susceptibility to Alzheimer’s disease. These are two important regions that are especially vulnerable to decline in Alzheimer’s, being the first to show amyloid plaque formation. When mice in the early stages of the disease were given this novel gene therapy procedure via a targeted brain injection, they had developed very little plaques over a 4 month period in contrast to the normal mice, who showed significant plaque formation. They also performed much better in memory tests too, with better object exploration and curiosity, 

Amyloid plaques are shown in green, and the glial cells are shown in red (microglia) and magenta (astrocytes). The image on the right shows a mouse cortex that received the gene therapy, with fewer amyloid plaques. Credit: Imperial College London

“Scientists harness the way lentivirus infects cells to produce a modified version of the virus, that delivers genes into specific cells. It is being used in experiments to treat a range of conditions from arthritis to cancer. We have previously successfully used the lentivirus vector in clinical trials to deliver genes into the brains of Parkinson’s disease patients”

When the researchers examined the brain more closely they also found that there had been no loss of cells in the hippocampus in that 4 month period, in contrast to the other group. There was also a marked reduction in glial cells which are typically raised in Alzheimer’s and release harmful inflammatory substances. 

“There are currently no treatments able to halt the progression of damage in Alzheimer’s, so studies like this are important for highlighting new and innovative approaches to take us towards that goal. This research sets a foundation for exploring gene therapy as a treatment strategy for Alzheimer’s disease, but further studies are needed to establish whether gene therapy would be safe, effective and practical to use in people with the disease. The findings support PGC-1-alpha as a potential target for the development of new medicines, which is a promising step on the road towards developing treatments for this devastating condition”

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