Alzheimer’s disease is the most common cause of dementia worldwide, accounting for nearly 80% of dementia cases. Currently, more than 6 million people in the United States alone are living with Alzheimer’s, with that number expected to rise to nearly 13 million by 2050. One of the biggest challenges facing Alzheimer’s patients is the need for a cure, which has yet to be found. While a cure is still yet to come, a group of Canadian researchers has successfully introduced a genetic mutation into human cells which they believe could open the doors for a potential preventative treatment for Alzheimer’s.
To better understand the implications of the team’s findings, let’s break the study down into pieces, starting with what this genetic mutation is, and how it could be used to prevent Alzheimer’s.
What Is This Genetic Mutation?
The breakthrough discovery, made by researchers from the Université Laval Faculty of Medicine and CHU de Québec–Université Laval Research Centre successfully identified a specific genetic mutation that could be used as a preventative treatment for Alzheimer’s disease. The mutation was first identified in 2012 in a small subset of the Icelandic population. Known as A673T, the Icelandic mutation appears to interfere with the formation of amyloid plaques that gum up the brains of people with Alzheimer’s disease, resulting in loss of memory and cognitive problems.
“It’s a very rare mutation,” says Professor Jacques-P. Tremblay, the study’s lead author, found in only 0.1% of Iceland’s population. “It’s a natural phenomenon and the people with this mutation appear to be capable of living a bit longer and there are no adverse effects from it.”
Using this knowledge, Tremblay and his team set out to edit the genes of humans without this mutation to see if they could create a preventative treatment for Alzheimer’s. This was done via a process commonly known as gene therapy.
What Is Gene Therapy?
In recent years, the term gene therapy has been used to describe several treatments or procedures that are not, in fact, gene therapy. The most noticeable of these instances are is the misinformation surrounding the COVID-19 vaccines, specifically the mRNA vaccines made by Pfizer and Moderna. False claims quickly spread throughout social media, claiming that the vaccines were a type of “gene therapy,” or that they could alter your DNA. Not only are these claims false, but they also have real-world consequences that can be deadly. So, before diving into the findings of the Canadian study, let’s first take a look at what gene therapy is, and what it isn’t.
Gene therapy is a broad term. In its most basic definition, it is used to describe an experimental technique that uses genes to treat or prevent disease. Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use. This type of replacement can be done in a variety of ways, the most common of which include:
- Replacing a disease-causing gene with a healthy copy of the gene
- Inactivating a disease-causing gene that is not functioning properly
- Introducing a new or modified gene into the body to help treat a disease
As it pertains to the Canadian study, scientists used an improved version of the gene-editing tool CRISPR to successfully edit human genomes to mimic an existing mutation that appears to protect against Alzheimer’s.
While gene therapy is a promising treatment option for many diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective.
How Can a Genetic Mutation Become a Preventative Treatment for Alzheimer’s Disease?
Tremblay believes the mutation could one day be used to preventively modify the genome of people who are more at risk of developing the disease. This includes those with a family history of the disease whose first symptoms of memory loss can appear at 35 or 40 years old.
The brains of those with Alzheimer’s present amyloid plaques, which have a level of toxicity believed to cause neuron death. These plaques are formed when the amyloid precursor protein is cleaved by an enzyme called beta-secretase. “The Icelandic mutation makes it harder for this enzyme to cleave the amyloid precursor protein. As a result, the formation of amyloid plaques is reduced,” explains Tremblay.
In theory, introducing the Icelandic mutation into the genome of people at risk of developing Alzheimer’s could prevent or slow the progression of the disease.
“Unfortunately, we can’t go back and repair the damage that caused neurons to die,” says Tremblay. “The treatment would therefore be particularly suitable for people from families affected by the hereditary form of the disease, which manifests itself in memory problems from the age of 35 to 40. If successful, it could also potentially be used to treat people with the most common form of Alzheimer’s, which occurs after age 65, at the earliest signs of the disease.”
“The challenge now is to find a way to edit the genome of millions of brain cells,” he says. “We are looking at different possibilities, including the use of non-infectious viruses, to deliver the editing complex inside neurons. Now that the proof of concept has been established in human cells in vitro, we will test this approach in mice that express Alzheimer’s disease. If the findings are conclusive, we hope to be able to conduct a small-scale study in people with mutations that cause the onset of Alzheimer’s at age 35 to 40.”
The study’s findings were published in The CRISPR Journal on February 7, 2022. While more research is needed in order to confirm the efficacy of the group’s findings, Tremblay and his team are confident that they have found a preventative treatment for Alzheimer’s.
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