The only treatments approved to treat Alzheimer’s are medications with limited effectiveness and a risk of serious, sometimes fatal, side effects. That’s why scientists are looking for therapies—especially those that don’t involve drugs—that can stop the disease.
An experimental therapy may slow the progression of symptoms, a small preliminary 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 visible. affected by the disease, according to the report presented on Thursday at the meeting of Clinical Trials in Alzheimer’s Disease in Madrid.
The researchers found that when the device was targeted to the right spot in the brain, it could slow the development of symptoms, such as memory loss, compared to inactive treatment.
In Alzheimer’s, neurons begin to malfunction, leading to symptoms of memory loss. Previous research has indicated 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, a professor of human physiology at the University of Ferrara and one from the co-founders of Sinaptica, the Cambridge, Massachusetts-based company currently developing the therapy.
“The goal is to restore connections between neurons by improving activity in certain areas relevant to the disease,” Koch said in a Zoom interview with our sister network NBC News. “This therapy is like training for neurons.”
The idea is that, just as exercise strengthens muscles, the electrical signals generated by TMS could improve the ability of neurons to make connections with each other.
About 6.9 million people suffer from Alzheimer’s 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 included 32 volunteers with Alzheimer’s, ages 56 to 88, who were followed for 52 weeks. Sixteen of the participants who received the treatment were women.
Initially, the researchers determined the exact point in the brain’s default neural network, which is involved in storing memories of life events, that would benefit most from electrical stimulation by using TMS to “alert.” When the electricity activated the correct point, a signal spread through the network, like the waves seen when a stone is thrown into a body of water.
Afterwards, 18 of the volunteers received weekly 20-minute sessions with TMS, while 14 received so-called sham treatments, in which participants were treated as if they were receiving TMS therapy, but without turning on the device, to rule out the placebo effect. . The TMS device was crucial to the research because it allowed electrical signals to be generated in the brain without any sensation.
“It would be almost impossible to use an 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 fairly uncommon and included mild headaches, skin discomfort, and neck pain.
When the two groups were compared using standard cognitive tests, researchers found that patients who received TMS therapy had a 44% slower rate of symptom worsening.
To put it in perspective, two of the newer drugs, lecanemab and donanemab, have been shown to moderately reduce the decline in memory and thinking abilities: 27.1% and 22.3%, respectively. The treatments are infusions of monoclonal antibodies given every two to four weeks and are expensive: between $26,500 and $32,000 per patient per year. Both are associated with an increased risk of brain swelling and microbleeds.
Additionally, during the year-long TMS trial, participants who received the experimental treatment showed less impairment in their abilities to perform activities of daily living. “That’s important not only for the patient, but also for the caregivers,” Koch said.
Koch and his colleagues are currently planning a Phase 3 trial, which would be necessary for approval by the Food and Drug Administration (FDA).
Dr. Irina Skylar-Scott, a cognitive neurologist and associate clinical professor at Stanford University’s Memory Disorders Center, called the procedure in the study promising. “As a field, we are all excited about new mechanisms and new pathophysiological targets.”
However, the research has important limitations. The size of the trial is small and was only conducted at one location.
“The next step is to do a multi-center phase 3 trial to see if this pays off,” added Skylar-Scott, who was not involved in the research. “If it works, it will be very exciting.”
The findings 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 worked better on several scales compared to sham treatment, which is good. But as in any study, the devil is in the details.”
Honig added that this is a small, single-center study. “A multicenter trial would offer a little more hope for generalization,” he said, meaning it could be applied to a broader group of people. Honig was not involved in the new study.
Honig would also like to see biomarker measurements in a future study, such as blood tests and brain scans to determine if there are real improvements in the disease, demonstrated, for example, by reductions in tau and/or amyloid in the brain, along with the reduction of symptoms.
As for what he would tell his patients: “Based on these results, not much can be said about the usefulness of these treatments.”
The idea behind the new research “is very interesting,” although limited by the small number of patients, said Dr. Ryan Darby, associate professor of neurology and director of the frontotemporal dementia clinic at Vanderbilt University Medical Center.
Another problem: It’s not yet clear whether this method will be easily adopted by other centers, said Darby, who was not involved in the TMS research. “But I think the results are exciting and worth investigating.”
