Fresh off positive data presented at the Clinical Trials on Alzheimer's Disease 2024 (CTAD) conference earlier this month, Sinaptica's CEO, Ken Mariash described neuromodulation in Alzheimer's as the start of a "renaissance" for this technology.

While neuromodulation has seen success in treating Parkinson's, depression, and other neurological disorders, Mariash highlights the vast potential for Alzheimer's in an exclusive interview with Medical Device Network.

Sinaptica's neuromodulation device, the SinaptiStim system, delivers targeted brain stimulation through a weekly, 20-minute session. The therapy specifically targets the "precuneus," a crucial region of the brain's default mode network (DMN) involved in memory and self-reflection. By stimulating this area, the therapy aims to enhance brain adaptability, reinforce memory pathways, and preserve cognitive connections.

Data presented at the CTAD 2024 conference from 29 October to 1 November in Madrid, Spain, highlighted that the system significantly slowed Alzheimer's progression over a 12-month Phase II study (NCT05454540) in 32 patients. Using the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) as a primary measure, patients in the neuromodulation group experienced an average CDR-SB change of 1.36 points compared to 2.45 in the placebo group - a 44% reduction in disease progression over one year.

One of the key aspects of Sinaptica's technology is the use of "perturbation-based biomarkers." By actively stimulating the brain and measuring its response, researchers gain detailed insights into individual brain function. "Typically, brain activity is recorded at rest, but to truly understand a complex system, you need to perturb it and then analyse how it reacts," explained Emiliano Santarnecchi, Sinaptica's scientific co-founder and associate professor of neurology and radiology at Harvard Medical School.

This process enables Sinaptica's team to "fingerprint" unique brain activity patterns, correlating them with symptoms and treatment response, paving the way for tailored neuromodulation strategies.

The approach also holds potential as a diagnostic and prognostic tool. "The idea of perturbation-based biomarkers initially started as a diagnostic biomarker concept," Santarnecchi said. "We can compare individual fingerprints' in patients and controls, identify who might respond to treatment, and predict disease trajectory. If I have a marker that tells me already that you're going to develop something ten years before, we could go into the preventative space and anti-aging."