About 5.7 million people in the United States alone are living with Alzheimer's disease, but doctors have been slow to develop treatments for the neurodegenerative condition. The disease, which is partially genetic in basis, is characterized by a build-up of protein plaques in the brain that kill neurons. A groundbreaking study on the genes that cause plaques to form, published just a week ago, shows promising progress toward effective therapy against the Alzheimer's gene.
The Alzheimer's gene is neutralized by science
In the paper, the researchers showed the results of an experiment in which they successfully neutralized a genetic risk factor for Alzheimer's disease in human neurons. The goal was to get rid of a protein called apolipoprotein E4 (ApoE4), which is known to play a role in plaque formation. They then took induced pluripotent stem cells that normally carry the gene for ApoE4, and then manipulated or edited that gene so that the cell manifests a different and less harmful form of the protein.
Their experiment worked, marking a first scientific discovery: it is proof of concept that this gene can be manipulated to reduce brain conditions that are less favorable for Alzheimer's. It is a minor but significant step towards developing gene therapies for people who have the Alzheimer's gene.
ApoE4 is considered a risk factor for Alzheimer's disease because it is associated with the formation of neurofibrillary tangles, made of phosphorylated tau protein. These, in turn, form the plaques that characterize Alzheimer's disease (they also form as a result of traumatic brain injury). But for many people living with Alzheimer's disease, their condition is at least partially due to an ApoE4-mediated genetic predisposition.
In the experiment, the scientists used gene editing to alter the expression of human neurons and cause them to create ApoE3 instead of harmful ApoE4. "Conversion of ApoE4 to ApoE3 by gene editing significantly reduced p-tau levels," they write. "Our findings (in human-induced pluripotent stem cell-derived neurons) provide proof of concept that correction of the pathogenic ApoE4 conformation is a viable therapeutic approach for ApoE4-related Alzheimer's disease."
By demonstrating the first instance of gene editing to decrease the damage of Alzheimer's disease, this study provides an important first step toward possible future therapies for people who show a genetic risk for Alzheimer's disease. Future studies are likely to try to identify other genes involved in the disease so that treatment can have a multiple approach.
Knowing which genes are involved in Alzheimer's disease opens up avenues for gene therapy, a form of treatment that involves inserting new genetic material into living cells through the use of viruses.
Joint discomfort is common and usually felt in the hands, feet, hips, knees, or spine. Pain may be constant or it can come and go. Sometimes the joint can feel stiff, achy, or sore. Some patients complain of a burning, throbbing, or “grating” sensation. In addition, the joint may feel stiff in the morning but loosen up and feel better with movement and activity. However, too much activity could make the pain worse.