According to a latest study published in Nature Medicine, researchers have successfully neutralize a gene associated with Alzheimer’s.
The gene, known as apoE4, has been associated with the build-up of the tau tangles and beta-amyloid plaques that are linked to the disease. Prior to the latest accomplishment, studies which have tried to look into this connection and attempted to create drugs have been resulted in disappointment as they have focused on mouse models rather than human cells.
Yadong Huang, the lead of the latest study explained, “Drug development for Alzheimer’s disease has been largely a disappointment over the past 10 years. Many drugs work beautifully in a mouse model, but so far they’ve all failed in clinical trials. One concern within the field has been how poorly these mouse models really mimic human disease.”
As a result, the group of researchers started using human cells in the lab and took skin cells from patients with Alzheimers who have two copies of apoE4 as well as samples from people with the normal variant known as apoE3, and turned them into stem cells.
After the scientists forced these cells to form human neurons, the researchers were able to study how t he apoE4 gene variant influences the build-up of the tau proteins and beta-amyloid plaques that are associated with the development of Alzheimer’s. After finding that yes, it does indeed cause this build-up to occur, they then wanted to know how: does the presence of apoE4 causing a loss of apoE3 function, or is it itself causing the toxic effects seen? These answers are vital as to how we might treat the problem.
Huang revealed, “If the damage is caused due to the loss of a protein’s function, you would want to increase protein levels to supplement those functions. But if the accumulation of a protein leads to a toxic function, you want to lower production of the protein to block its detrimental effect.”
Interestingly, the lab grown neurons were able to prove that the presence of apoE4, rather than absence of absence of apoE3, caused the damaging proteins to build-up in the cells. This meant that the researchers could use earlier work they had done in altering the abnormal apoE4 gene to resemble the innocuous apoE3 gene, using what are called “structure correctors.”
By targeting the gene in this way, they were in effect able to neutralize it and restored normal function to the neurons. They now hope to work with drug companies to see if they are able to translate what they found into a treatment that can then be put through clinical trials.