According to the National Institute of Aging, Alzheimer’s disease is currently ranked as the sixth leading cause of death in the United States and recent estimates indicate the disorder may rank third, just behind heart disease and cancer, as the leading cause for older people. Over 100 years ago, the disease was identified by Dr. Alois Alzheimer, and in the century since its initial discovery – which has seen $480 million spent per year on research – we are still far from a cure.
Despite significant efforts, progress has been slow. In April of this year, Gladstone Institutes published a paper in Nature Medicine showcasing substantial findings: researchers were able to change a protein commonly associated with Alzheimer’s disease – the apoE4 gene – into a less harmful form, apoE3. According to the study, having one apoE4 gene more than doubles one’s chances of developing Alzheimer’s, and possessing two copies of the gene makes it 12 to 15 times more likely. Using stem cells from Alzheimer’s patients who had two copies of the apoE4 gene and stem cells from healthy volunteers who also had a pair of the less harmful apoE3 gene, researchers were able to identify exactly why apoE4 puts individuals at such increased risk for Alzheimer’s disease and then change the problematic gene into a harmless one. The finding may also solve a problem that has long plagued Alzheimer’s research: most mice models fail in clinical trials because they don’t mimic a human environment. Gladstone Institutes found that amyloid-β production, which is strongly associated with Alzheimer’s, is not affected by the ApoE4 gene in mice, so mouse models don’t address ApoE4-related forms of Alzheimer’s in humans. With this study, researchers were able to clearly show the impact of this single gene on Alzheimer’s-related pathologies by using gene editing tools in human brain cells.
The identification of this harmful gene and the understanding of how to transform it into a harmless one is a huge milestone in Alzheimer’s research and certainly one to be celebrated. Unfortunately, the likelihood of this research being replicated, passing clinical trials and actually reaching patients suffering from the disease is slim. Uncovering these genetic discoveries – identifying apoE4, understanding how it is linked to Alzheimer’s and negating its effects – is incredibly important, yet the research process remains expensive, inefficient, time consuming and unpredictable. Furthermore, it could be decades before the results of this research can be translated into relevant clinical therapies.
So how can we speed up the timeline for a cure? Rather than double the time and money we invest in research, we may need to rethink our approach. Due to recent advancements in gene editing, we can now generate models for diseases such as Alzheimer’s with much greater efficiency and within a reasonable time frame using a single tool: CRISPR, a revolutionary technology enabling scientists to precisely target and edit genetic material. Think of CRISPR as a pair of scissors empowering scientists to create custom cell lines with specific genetic changes and allowing for better insight into complicated genetic modifications associated with disease.
While a hugely powerful research tool, the learning curve of CRISPR can be steep, best practices have yet to be developed and as a result, adoption rates remain low. This technology is in high demand, but without industry standards, it will be difficult for it to reach its full potential – we need to make CRISPR and gene editing more accurate, efficient and accessible. With greater access to CRISPR tools and technologies, scientists can focus more on their research questions and experiments, and less on method development to build models for the disease. Research findings – such as those brought to light by Gladstone Institutes – can lead to action. We are sitting on a wealth of potential knowledge and – in the medical world – cures.
Kevin Holden is head of synthetic biology at Synthego
