A Phase 2 randomized, double-blind, sham-controlled trial of personalized repetitive transcranial magnetic stimulation (rTMS) has demonstrated promising results in slowing the progression of Alzheimer's disease (AD). The study, conducted by Sinaptica Therapeutics, showed that personalized rTMS applied over the precuneus (PC), a critical region within the default mode network (DMN), met its primary endpoint of change from baseline at 52 weeks on the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) in patients with mild-to-moderate AD.
The trial also achieved statistically significant results in key secondary endpoints, including changes in the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), Mini Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). These findings 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.
Giacomo Koch, MD, PhD, director of the Non-Invasive Brain Stimulation Laboratory at Santa Lucia Foundation, presented the 12-month data at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference. He noted, "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."
The study's results highlight the potential of rTMS as a noninvasive treatment strategy for AD, particularly given the functional changes frequently observed in the precuneus of AD patients. The combined use of TMS and EEG shows promise in enhancing the precision and efficacy of this intervention. Furthermore, the safety profile of personalized TMS suggests its potential for use alongside pharmacological treatments.
Emiliano Santarnecchi, PhD, an associate professor of neurology at Harvard Medical School, emphasized the potential of personalized TMS alongside pharmacological treatments, given its safety profile. The trial reported no serious adverse events, reinforcing the feasibility of integrating rTMS into existing AD treatment regimens.
Ken Mariash, CEO at Sinaptica, and the scientific cofounders of Sinaptica, Koch and Santarnecchi, discussed the key outcomes of the Phase 2 trial on personalized TMS in patients with AD at CTAD 2024.
