When it comes to neurodegenerative diseases, treatment implies a systemic and permanent process. Gene therapy offers a one-time intervention that can slow down and even stop the disease. How viable is this technique?

The peculiarity of the human brain and consciousness is that both elements develop when systematically included in the work. Lifestyle, habits, outlook on life – all this sums up with each other and allows a person to acquire more opportunities. Including in the treatment of diseases.

Gene therapy to improve brain function

Researchers developed a single dose of genetic therapywhich eliminates protein blockages that cause motor neuron disease. As a result of this defect, amyotrophic lateral sclerosis and frontotemporal dementia develop. These are two incurable neurodegenerative diseases that eventually lead to death.

The nature of the disease

Healthy neurons naturally produce “DNA-binding protein TAR 43”, abbreviated as TDP-43. This protein is essential for the healthy functioning of neurons. However, TDP-43 can change after synthesis, which leads to its accumulation and concentration in the “wrong” part of cells, which interferes with their normal work.

These accumulations are associated with devastating neurodegenerative diseases such as motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, and frontotemporal dementia (FMD).

BDN is a rapidly progressive disease that affects the ability of the brain and spinal cord to interact with the muscles, causing weakness that only increases over time. KDL is a group of disorders that are accompanied by the loss of neurons in the frontal and temporal lobes of the brain. This causes impaired behavior, personality breakdown, and/or difficulty speaking or understanding language. Both diseases are incurable and eventually lead to death. And even restoration of brain stem cells will not be an adequate solution here.

First steps and theoretical basis

Having for the first time revealed the mechanism of accumulation of pathological TDP-43 in BDN and LVS, researchers from Macquarie University in Sydney designed a genetic therapy that allows to remove the blockade and prevent the re-formation of the proteins.

We found for the first time that where abnormal TDP-43 accumulates, there is also an increase in 14-3-3 protein. The two proteins interact, which leads to their accumulation in cells. We were able to isolate a short peptide that controls this interaction, and we used it to create CTx1000.

Lars Ittner, co-author of the study.

The researchers found that a single dose of CTx1000 only affected the “bad” TDP-43 in mice, leaving the healthy version alone. It was not only safe, but also effective, even if symptoms were present at the time of treatment. After all, as we know, you can only slow or stop Alzheimer’s diseaseBut we are not talking about the regeneration of neural connections.

Importantly, CTx1000 targets only the pathological TDP-43, allowing it to make a healthy version of the protein and do its job unhindered. When we injected it in the lab, it dissolved the build-up by targeting TDP-43 proteins for recycling in the body and preventing new ones from forming.

Lars Ittner, co-author of the study.

How close is gene therapy for neurodegenerative diseases?

It may seem like the research in question was done just a few days ago. But it actually took Macquarie University researchers 15 years to get to this point. According to Yazi Ke, the study leader and a co-author, the results obtained were achieved years earlier in a laboratory setting. The scientists then discovered how CTx1000 stopped the progression of BDN and LVS even at very late stages and eliminated the behavioral symptoms associated with LVS.

We very much hope that when it goes to human trials, it will not only prevent people from dying from both BDN and LVS, but even allow patients to regain some of their lost function through rehabilitation.

Yazi Ke, leader and co-author of the study.

Since researchers have studied various mutations in TDP genes in the laboratory, gene therapy may find application in the context of other neurodegenerative diseases. What is the opportunity to forget? genetic development of cognitive skills.

We wanted to prove beyond a shadow of a doubt that this would work in a variety of situations, and would lead to clear improvement in both symptoms and changes in brain pathology. Although we are initially focusing on BDN and LVS, about 50 percent of Alzheimer’s cases also demonstrate TDP pathology, so it is possible that this treatment could be scaled to other neurodegenerative conditions in the future.

Annika van Hummel, co-author of the study.

What do you think? Ray Kurzweil bet on the year 2040 as the beginning of the technological Singularity, when progress will be exponential. But by then, technology will be more accessible, and the potential for human enhancement will be widespread.