Those who have someone in their life with Alzheimer’s know how devastating it is. The loss of memories which we hold so dear is a shock to the heart. If this weren’t bad enough, is it shattering to see their mental capabilities waste away, as there is no cure or any way to slow its progression. Even more fearful for some, Alzheimer’s carries with it a genetic component.
Five million people in the US today struggle with Alzheimer’s, according to a 2013 CDC estimate, and approximately 47 million globally are stricken, this being the most common form of dementia. Healthcare systems are set to take a beating financially, if not crumble outright in oncoming years as a tidal wave of seniors, who are likely to be diagnosed with Alzheimer’s, begin needing care.
So what causes Alzheimer’s? It starts when amyloid beta peptide, sticky plaques which invade the brain. These snap connections between neurons and choke them to death. As the buildup continues, it moves throughout the organ hollowing it out. These plaques are helped by another protein, tau tangles, which are strands that block proper nutrients from getting to affected areas.
How Alzheimer’s effects the brain.
Alzheimer’s usually takes root in the cortex first. Then it moves on to the hippocampus. These areas are responsible for memory and cognition. The cortex controls reasoning skills, thinking, mood, and long-term memory. The hippocampus is responsible for memory formation, orientation, learning, and transferring short-term memories into the long-term region. Damage to the cortex may make a person forget a recent conversation, while damage to the hippocampus will make them forget how they got home from an appointment.
Usually, Alzheimer’s begins in the cortex and spreads out from there, engulfing the hippocampus and then other areas. At the onset, symptoms may look like regular, age-related forgetfulness. Oftentimes, Alzheimer’s starts way before the disease is readily present, perhaps a decade or two before symptoms are recognized or felt.
Now researchers at Imperial College London have come up with a novel approach, a form of gene therapy delivered by a virus. If all goes well, it may act as a vaccine—protecting patients from developing Alzheimer’s, as well as a cure in the early stages. Viruses enter cells and write their own genetic code into them, in order to replicate. For gene therapy, manipulated viruses write the selected gene into the DNA of targeted cells. The gene used in this research is called PGC1-alpha, which plays a role in fat and sugar metabolism. It resists amyloid beta peptides.
If you want to try and goose such benefits yourself, try a little red wine, and perhaps some exercise—though not at the same time. Resveratrol is a compound found in wine that may increase the expression of this gene, though perhaps not enough to prevent Alzheimer’s outright. So far, this method of gene therapy has been successful in lab tests on mice.
Based on previous work in the lab, scientists discovered that the gene would resist the development of amyloid beta plaques. The lentivirus vector was used in this study, a type which is quickly becoming the workhorse of gene therapy, as it is being used in other trials to treat cancer, arthritis, and even Parkinson’s disease.
Model of gene therapy. Public Domain.
In this study, two groups of mice, one healthy and another with early-stage Alzheimer’s but where amyloid plaques had not yet formed, were used. Half of the group received two injections each, containing the engineered virus. One injection went into the cortex and the other the hippocampus. The other cohort stood as a control group. Researchers examined the mice four months after the therapy took place.
Those who were injected saw very little amyloid plaque development. The hippocampus in each was still intact. Meanwhile, in the control group, a large buildup of plaque was present. Another remarkable find, there were less glial cells present. These may aid the development of Alzheimer’s by releasing toxins which cause inflammation inside the brain, leading to further damage.
Researchers also included a memory test. They would place well-known objects into the mouse cages, alongside a new one. Those who didn’t have memory damage spent more time examining the new object and generally, acting as normal mice would.
Senior author Dr. Magdalena Sastre said that although the outcome was heartening, there are many hurdles yet to overcome. For one, the only way to administer the gene therapy currently, is a direct injection into the brain. A different delivery method would be required for it to be viable in humans. Though it was successful in mouse models, that doesn’t necessarily mean humans will respond the same way.
Even so, this is a successful proof-of-concept study which will see more investigation, and might someday, years from now, make it to a clinical setting near you. Investigators believe the treatment should work best when given in the early stages of Alzheimer’s, such as when symptoms first begin to appear.
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