The Promise of Personalized Neurostimulation in Slowing Alzheimer Progression: Giacomo Koch, MD, PhD; Ken Mariash; Emiliano Santarnecchi, PhD

WATCH TIME: 5 minutes

“We’re not only slowing cognitive decline, but we’re also seeing improvements in daily functioning and behavioral symptoms, which is profoundly beneficial for both patients and caregivers.”

In the field of neurology, repetitive transcranial magnetic stimulation (rTMS) targeting the default mode network (DMN) has gained recognition as a promising noninvasive treatment strategy for Alzheimer disease (AD). Recent studies have shown that patients with AD frequently exhibited functional changes in the precuneus (PC), which is known as a critical region within the DMN. Newly presented 12-month data from Sinaptica Therapeutics’ phase 2 randomized, double-blind, sham-controlled trial of personalized rTMS applied over the PC showed that the treatment met the primary end point as well as the secondary end points with no serious adverse events reported in patients with mild-to-moderate AD.^1,2

The trial’s primary end point was change from baseline at 52 weeks on the Clinical Dementia Rating Scale–Sum of Boxes while secondary end points included changes in the Alzheimer’s Disease Assessment Scale– Cognitive Subscale, Mini Mental State Examination, Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale and Neuropsychiatric Inventory. Presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held October 29 to November 1, in Madrid, Spain, by senior author Giacomo Koch, MD, PhD, director of the Non-Invasive Brain Stimulation Laboratory at Santa Lucia Foundation, the results suggest that personalized rTMS of the DMN may slow down the impairment of cognitive functions, activities of daily living, and behavioral disturbances in this patient population.

At CTAD 2024, scientific cofounders of Sinaptica, Koch and Emiliano Santarnecchi, PhD, as well as Ken Mariash, CEO at Sinaptica, sat down with NeurologyLive^® to dive deeper into the discussion on the key outcomes of the phase 2 trial on personalized TMS in patients with AD. Koch, who also serves as the professor of physiology at University of Ferrara, and colleagues, talked about how the combined use of TMS and EEG shows promise to enhance the precision and efficacy of this intervention. Furthermore, Santarnecchi, an associate professor of neurology at Harvard Medical School, and the director of the Precision Neuroscience & Neuromodulation Program at Massachusetts General Hospital, spoke about the potential personalized TMS has for use alongside pharmacological treatments, given its safety profile.

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REFERENCES
1. Casula E, Bonni S, Maiella M, et al. Results of a 52-Week Phase II Trial of Repetitive TMS of the Default Mode Network in Mild to Moderate Alzheimer’s Disease. Presented at: 2024 CTAD; October 29-November 1; Madrid, Spain. OC24.
2. Personalized Neuromodulation Treatment Significantly Slowed Alzheimer’s Progression in 12-month Phase 2 Study, Meeting Primary and Key Secondary Endpoints. News Release. Published October 31, 2024. Accessed November 5, 2024. https://sinapticatx.com/personalized-neuromodulation-treatment-significantly-slowed-alzheimers-progression-in-12-month-phase-2-study-meeting-primary-and-key-secondary-endpoints/