Sinaptica Therapeutics' neuromodulation device, SinaptiStim, has demonstrated promising results in a Phase II clinical trial for Alzheimer's disease. The trial met both its primary and key secondary endpoints, suggesting a potential new approach to slowing the progression of this debilitating condition.
Targeting the Brain's Default Mode Network
The SinaptiStim system employs tailored brain stimulation to target specific areas, particularly the praecuneus, a key component of the brain's default mode network (DMN). Each session lasts 20 minutes and is administered weekly. The therapy aims to enhance brain adaptability and strengthen memory pathways by stimulating this area, ultimately helping to preserve and reinforce neural connections.
Phase II Trial Results
Data presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference revealed that the SinaptiStim system significantly slowed Alzheimer’s progression over the 12-month Phase II study (NCT05454540), which involved 32 patients. The company is now moving forward with plans to initiate a Phase III study next year based on these positive findings.
Using the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) as the primary outcome measure, patients in the neuromodulation group exhibited an average CDR-SB change of 1.36 points, compared to 2.45 in the placebo group. This represents a 44% reduction in disease progression over the one-year period. Secondary measures also indicated improvements, with treated patients showing stability in daily activities (measured by ADCS-ADL) and enhanced cognitive and behavioral scores.
Building on Previous Studies
This study expanded upon a prior six-month trial (NCT3778151), extending the therapy to 12 months for 31 original participants while maintaining blinding to their treatment arms. An additional 17 patients were randomized, though 16 were lost to follow-up. Ultimately, 32 patients completed the 12-month trial.
Expert Commentary
Sinaptica’s scientific co-founder, Giacomo Koch, stated, “These latest results provide new additional evidence at 12 months, building on our prior positive six-month Phase II study, supporting the potential for nDMN to slow the impairment of cognitive functions, preserve activities of daily living, and reduce behavioural disturbances in Alzheimer’s patients, with no significant side-effects.”
Regulatory Pathway
Sinaptica, based in the US, has outlined a regulatory strategy for SinaptiStim. The device received Breakthrough Device designation from the US Food and Drug Administration (FDA) in October 2022.
The Future of Neuromodulation in Alzheimer's Treatment
Neuromodulation is emerging as a potential alternative treatment option for diseases such as Alzheimer’s, Parkinson’s, migraine, and depression. Howard Fillit, chief scientific officer of the Alzheimer’s Drug Discovery Foundation, suggests that future novel therapeutics may involve “a component of combination therapy and precision therapy strategy, aimed at slowing the progression or stopping the onset of Alzheimer’s altogether.”
GlobalData estimates the global neuromodulation device market will reach $11.4 billion by 2033, up from $6 billion in 2022.
