Medication with little efficacy and a high risk of serious, occasionally fatal adverse effects is the sole licensed therapy for Alzheimer’s disease. For this reason, researchers look for treatments that might halt the illness, particularly those that don’t use medication.
According to a modest early trial, one investigational medication may reduce the progression of symptoms. According to a report presented Thursday at the Clinical Trials in Alzheimer’s Disease meeting in Madrid, researchers were able to target a key brain network that is involved in storing memories and is typically hit hard by the disease by using a transcranial magnetic stimulation (TMS) device, which is widely used to treat depression and other mental illnesses safely.
Compared to a passive therapy, researchers discovered that the device might slow the onset of symptoms like memory loss when it was directed to the correct location in the brain.
Alzheimer’s disease causes the crippling symptoms of memory loss because nerve cells in the brain eventually begin to malfunction. According to earlier studies, the buildup of two abnormal proteins, tau and beta-amyloid, impairs neurons’ capacity to maintain and create new connections, according to Dr. Giacomo Koch, a professor of human physiology at the University of Ferrara and a co-founder of Sinaptica, the Cambridge, Massachusetts-based company that is currently working on the treatment.
In a Zoom interview with NBC News, Koch stated, “The objective is to restore connections between neurons by enhancing activity in certain areas relevant to the disease.” “This treatment is similar to neuronal training.”
According to the theory, the electrical impulses produced by the TMS may improve neurons’ capacity to interact with one another, much like exercising improves muscles.
In the United States, 6.9 million people suffer with Alzheimer’s. By 2060, the figure may rise to 13.8 million, according to the Alzheimer’s Association.
32 Alzheimer’s disease volunteers, ages 56 to 88 at the beginning of the study, participated in the new study, a phase 2 clinical trial, and were monitored for 52 weeks. Women made up sixteen of the individuals that received the therapy.
Using TMS to “ping” several areas, the researchers first identified the precise location in the brain’s default mode network—which is important in storing memories of life events—that would most benefit from electrical stimulation. A signal would go across the network like ripples when a stone is thrown into a body of water after the energy pushed the appropriate area into action.
In order to rule out the placebo effect, 14 volunteers underwent so-called sham treatments, in which they were treated as though they were receiving TMS therapy but without the device being switched on. Meanwhile, 18 volunteers had weekly 20-minute sessions with the TMS. Because it made it possible to create electrical impulses in the brain without feeling, the TMS device was essential to the study.
“Using an electrical current would be extremely painful, making it nearly impossible,” Koch stated. “In this instance, we can create strong electrical currents in the brain by using extremely strong magnetic fields, which are safe and well tolerated.”
Mild headaches, skin irritation, and neck pain were among the relatively rare side effects.
Standard cognitive tests were used to compare the two groups, and the researchers discovered that patients undergoing TMS treatment experienced a 44% slower rate of symptom worsening.
Lecanemab and donanemab, two of the more recent drugs, have been demonstrated to somewhat reduce a deterioration in memory and cognitive function, by 27.1% and 22.3%, respectively, to put that into context. Monoclonal antibody infusions are the therapies, which are administered every two to four weeks and cost between $26,500 and $32,000 annually per patient. Both are linked to a higher risk of microhemorrhages and brain edema.
Furthermore, those who received the experimental therapy during the year-long TMS study had no deterioration in their capacity to carry out daily living tasks. Koch stated, “That’s important for caregivers as well as the patient.”
A phase 3 trial, which would be required for Food and Drug Administration approval, is presently being planned by Koch and his colleagues.
The method in the research shows promise, according to Dr. Irina Skylar-Scott, a clinical assistant professor and cognitive neurologist at Stanford University’s Center for Memory Disorders. “We are all enthusiastic about new pathophysiological targets and mechanisms as a field.”
Nevertheless, the research has serious drawbacks. There was only one location and a limited trial size.
Skylar-Scott, who was not involved in the study, stated, “The next step is to do a phase 3 trial across multiple centers to see if this bears fruit.” “It will be really exciting if it works.”
According to Dr. Lawrence Honig, a neurology professor at Columbia University Irving Medical Center, the results are “very, very preliminary.” According to the data, it performed better than the sham therapy on a number of scales, which is positive. However, the specifics are crucial in any study.
According to Honig, the study is modest and only involves one center. He went on to say, “A multicenter trial would offer a little more hope of generalizability,” which means it may be applicable to a larger population. The new research did not include Honig.
In order to ascertain whether there are real improvements in the condition, as evidenced, for instance, by decreases in tau and/or amyloid in the brain, as well as a reduction in symptoms, Honig would also like to see assessments of biomarkers in a future trial, such as blood tests and brain scans.
“On the basis of these results you can say much about the utility of these treatments,” he would advise his patients.
Dr. Ryan Darby, an assistant professor of neurology and head of the frontotemporal dementia clinic at the Vanderbilt University Medical Center, described the new study’s concept as “very cool,” despite the small number of patients.
Another problem: Darby, who was not involved in the TMS study, stated that it is still unclear if other centers will find it easy to use this approach. “However, I believe the outcomes are intriguing and worthwhile.”
