Tackling Alzheimer from within the brain

Gene therapy might be the key to protection

Making brains generate their own therapeutics could be a promising approach to slowing or even stopping the progression of Alzheimer’s disease. Researcher Niels Reinders has shown in lab experiments that this approach could work. Now, he’s focused on turning this idea into a treatment that could help millions of people worldwide.

Dr. Niels Reinders
Dr. Niels Reinders (© LegHetVast / RTL4)

Alzheimer’s disease has been a difficult challenge for doctors and scientists for decades. They expect the number of Alzheimer’s patients to double or even triple by 2050. The disease, which severely affects memory and other brain functions, seems unstoppable.

Many researchers trying to combat the disease focus on a protein called amyloid beta. People with Alzheimer’s have high levels of this protein, which clumps together and harms brain cells. The idea is that by targeting amyloid beta, the disease can be controlled. However, even though there has been some progress, no major breakthroughs have been made, and a cure still seems far off.

Protecting connections

Niels Reinders
Dr. Niels Reinders (© LegHetVast / RTL4)

Cell biologist Niels Reinders and his team decided to try a new approach. Instead of focusing on amyloid beta, they look at the connections between brain cells, called synapses. These synapses are crucial for brain function, and in people with Alzheimer’s, they gradually disappear, leading to cognitive decline. Reinders believes that by protecting these connections, the brain can keep functioning despite the disease.

Protective mini-proteins

Reinders’ strategy involves using mini-proteins called peptides, specifically PTEN-PDZ and GluA23y, which help keep synapses from being damaged. In animal studies, these proteins have shown promise in reducing the cognitive symptoms of Alzheimer’s.

Delivery problem

The problem is that you can’t just inject these peptides into the brain. The brain has a protective barrier called the blood-brain barrier, which blocks harmful substances – and unfortunately, these peptides can’t get through either.

Injecting the proteins into the brain isn't an option because the peptides are unstable and break down quickly. Such an invasive injection would need to be done very often, probably several times a day, and could also cause permanent damage to brain cells.

A big advantage of this approach is that the body’s own DNA remains unchanged.

The solution may be to make the brain produce these protective proteins itself. This can be done by giving brain cells a genetic code that tells them to make the proteins. The code is delivered by harmless viruses that can cross the blood-brain barrier. Once the brain cells carry the extra genetic code, they start producing the protective proteins.

“A big advantage of this approach is that the code is placed next to the cell's own DNA,” says Reinders. “Therefore, the body’s own DNA remains unchanged.”

Promising results

In lab tests, Reinders’ team got brain cells from rats to produce these mini-proteins. When exposed to harmful proteins associated with Alzheimer’s, the brain cells were protected, and their synapses stayed intact. These cells came from the hippocampus, the part of the brain that Alzheimer’s disease often affects first.

The results are encouraging, but Reinders and his team are continuing their research to understand exactly how this process works and how to make the brain produce the proteins more effectively. Their goal is to develop a treatment that can slow down or even prevent Alzheimer’s.

My dream is that we can one day treat Alzheimer’s with just one therapy, and I believe my research is bringing us closer to that goal

Personal motivation

In a new episode of the Dutch tv show Briljante Breinen (in English: Brilliant Minds), Reinders shares not only his research but also his personal relationship towards the disease. Shortly after he started studying Alzheimer’s, his mother was diagnosed with the disease. Watching his mother go through it has given him extra motivation to find solutions that could make a difference.

“My dream is that we can one day treat Alzheimer’s with just one therapy,” says Reinders. “And I believe my research is bringing us closer to that goal.”

The episode of Briljante Breinen featuring Niels Reinders aired on RTL 4 on 13 October 2024. It’s also available on the streaming service Videoland. The show is in Dutch and does not provide English subtitles. Below you can watch a preview of this episode.