Scientists studying Alzheimer’s disease say it’s likely the brain’s design could delay symptoms

Linda Carroll and Mustafa Fattah –NBCNews

The only treatments approved for Alzheimer’s disease are drugs with limited effectiveness and a risk of serious, sometimes fatal, side effects. That’s why scientists are looking for treatments, especially those that don’t involve drugs that can stop the disease.

Experimental therapy may slow symptom progression, a small pilot study suggests. Using a transcranial magnetic stimulation (TMS) device, which is often used to safely treat depression and other mental illnesses, the researchers were able to target a key brain network that is involved in storing memories and is often seen as highly affected. According to a report presented Thursday at a meeting of Alzheimer’s disease clinical trials in Madrid.

Researchers have found that when the device targets the right spot in the brain, it can slow the development of symptoms such as memory loss compared to inactive treatment.

In Alzheimer’s disease, neurons begin to malfunction, leading to symptoms of memory loss. Previous research has shown that the accumulation of two aberrant proteins, beta-amyloid and tau, impairs the ability of neurons to form new connections and maintain existing ones, explained Dr. Giacomo Koch, professor of human physiology at the University of Ferrara and one of the researchers. from the co-founders of Sinaptica, the Cambridge, Massachusetts-based company currently developing this therapy.

“The goal is to restore connections between neurons by improving activity in specific areas relevant to the disease,” Koch said in a Zoom interview with our sister network NBC News. “This therapy is like training neurons.”

The idea is that, just as exercise strengthens muscles, the electrical signals generated by TMS can improve the ability of neurons to make connections with each other.

About 6.9 million people suffer from Alzheimer’s disease in the United States. That number could reach 13.8 million by 2060, according to the Alzheimer’s Association.

The new study, a phase 2 clinical trial, initially enrolled 32 volunteers with Alzheimer’s disease, ages 56 to 88, who were followed for 52 weeks. Sixteen of the participants who received treatment were women.

(Limiting sugar intake before age 2 reduces risk of diabetes and hypertension, study finds)

The researchers initially identified the precise point in the brain’s standard neural network, which is involved in storing memories of life events, that would benefit most from electrical stimulation, using TMS for the “warning.” When electricity activates the correct point, a signal is given. spread through the network like the waves seen when a stone is thrown into a pond.

Afterwards, 18 volunteers received weekly 20-minute TMS sessions, and 14 received what is known as sham treatment, in which participants are treated as if they were receiving TMS therapy but without the device being turned on to eliminate the placebo effect. . The TMS device was critical to the study because it allowed electrical signals to be generated in the brain without any sensation.

“It would be almost impossible to use electric current because it would be very painful,” Koch said. “In this case, we can use very powerful magnetic fields, which are very well tolerated and safe, to induce strong electrical currents in the brain.”

Side effects were quite rare and included mild headaches, skin discomfort and neck pain.

When the two groups were compared using standard cognitive tests, the researchers found that patients receiving TMS therapy had a 44% slower rate of symptom worsening.

By comparison, two new drugs, lecanemab and donanemab, were shown to moderately reduce decline in memory and thinking abilities: 27.1% and 22.3%, respectively. The treatment is an infusion of monoclonal antibodies every two to four weeks and is expensive: $26,500 to $32,000 per patient per year. Both are associated with an increased risk of cerebral edema and microhemorrhages.

(A particular danger is breast cancer recurrence. New research aims to prevent this scenario.)

Additionally, in a one-year TMS study, participants receiving the experimental treatment had less impairment in their ability to perform daily activities. “This is important not only for the patient, but also for the caregivers,” Koch said.

Koch and his colleagues are currently planning a phase 3 study, which is necessary for approval by the Food and Drug Administration (FDA).

Dr. Irina Skylar-Scott, a cognitive neurologist and clinical assistant professor at the Memory Disorders Center at Stanford University, called the study procedure promising. “As an industry, we are all excited about new mechanisms and new pathophysiological targets.”

However, the study has important limitations. The study size is small and was conducted in only one location.

“The next step is to do a multicenter phase 3 study to see if it pays off,” added Skylar-Scott, who was not involved in the study. “If it works, it will be very interesting.”

The results are “very, very preliminary,” said Dr. Lawrence Honig, a professor of neurology at Columbia University Irving Medical Center. “At first glance, if you look at the numbers, it performed better than the sham treatment on several scales, which is good. But, as with any research, the devil is in the details.”

Honig added that this is a small, single-center study. “A multicenter study would give a little more hope of generalizability,” he said, meaning it could be applied to a larger group of people. Honig was not involved in the new study.

Honig would also like to see biomarker measurements in future studies, such as blood tests and brain scans, to determine whether there are real improvements in the disease, demonstrated by, for example, a decrease in tau and/or amyloid in the brain, as well as a decrease in symptoms.

As for what he told his patients: “Based on these results, little can be said about the usefulness of these treatments.”

The idea behind the new study is “very interesting,” although limited by the small number of patients, said Dr. Ryan Darby, assistant professor of neurology and director of the frontotemporal dementia clinic at Vanderbilt University Medical Center.

Another concern: It’s unclear whether the technique will be easily adopted by other centers, says Darby, who was not involved in the TMS study. “But I think the results are impressive and worth studying.”