Gene Therapy Breakthrough Could Prevent and Treat Alzheimer's
Researchers have successfully converted a high-risk gene associated with Alzheimer's into a lower-risk version in laboratory cell cultures, offering a potential new therapeutic avenue.
Researchers at the University of Bristol have developed a gene therapy technique that could offer a new way to prevent and treat Alzheimer's disease. The team successfully converted the APOE4 gene, a significant genetic risk factor for Alzheimer's, into the lower-risk APOE3 gene within human cells.
Alzheimer's disease is the most prevalent form of dementia, accounting for approximately 60% of dementia cases in the UK. While the exact cause of the condition remains unknown, genetic factors, particularly variations of the APOE gene, play a crucial role in an individual's risk. Everyone inherits two copies of the APOE gene, one from each parent. The APOE3 variant is the most common and is associated with normal protein function. However, approximately one in four individuals carries at least one copy of the APOE4 gene, which has been linked to an increased risk of developing Alzheimer's. About one in 50 people have two copies of the APOE4 gene.
Having the APOE4 gene does not guarantee the development of Alzheimer's. Lifestyle factors such as physical activity and social engagement are known protective measures. Nevertheless, individuals with one copy of APOE4 face double the risk of developing Alzheimer's compared to the average, while those with two copies face approximately ten times the risk. The APOE4 gene may also be associated with an earlier or more severe diagnosis.
Dr. Kevin Kemp, a neuroscientist at the University of Bristol and lead author of the study, explained that the APOE4 and APOE3 genes are nearly identical, differing by only a single letter in their genetic code. This minute difference, however, significantly alters the protein produced by the gene, impacting its role in maintaining brain cell health and clearing toxic proteins like amyloid beta, which is strongly implicated in Alzheimer's.
The research team utilized a technique that chemically modifies a specific part of the genetic code. This modification leverages the cell's natural repair mechanisms to make the change permanent. In their experiments, they converted APOE4 to APOE3 in immune cells derived from individuals with Alzheimer's. A modified virus was used as a delivery system for the new genetic code into these cells. The researchers found minimal unintended alterations to the cells' broader DNA.
The proposed therapeutic strategy involves these modified immune cells entering the brain and releasing the APOE3 protein. This protein would then be absorbed by nerve cells and other brain cells involved in Alzheimer's progression, counteracting the detrimental effects of the APOE4 gene. The findings have not yet been published in a peer-reviewed journal, but Dr. Kemp anticipates publication and hopes for clinical trials in humans within five to ten years.
This potential therapy could theoretically be administered as a one-off injection, targeting either individuals already exhibiting Alzheimer's symptoms or those identified as carriers of the APOE4 gene for preventative purposes. A significant hurdle remains, as genetic testing for APOE4 is not widely available on the NHS, limiting awareness of this genetic risk factor for many.
Experts in the field view this research as a promising development. Katharina Cosker, research programmes manager at Alzheimer's Research UK, noted that this study reflects a broader push to understand Alzheimer's underlying biology, especially as new disease-modifying treatments emerge. She highlighted that novel approaches targeting genetic risk factors could broaden treatment options, particularly for those who may not benefit from current therapies.
Dr. Richard Oakley, associate director of research and innovation at the Alzheimer's Society, described the early-stage research as an "exciting glimpse" into the future of Alzheimer's treatment. However, he cautioned that it is still laboratory research in cells, and its safety and efficacy in humans are yet to be determined. "With around one million people in the UK living with dementia, we urgently need treatments that can slow it more effectively, stop it progressing or prevent it altogether," he stated.