Sinaptica Therapeutics is exploring repetitive transcranial magnetic stimulation (rTMS) as a novel approach to combat Alzheimer's disease. A recent Phase 2 trial indicates that personalized rTMS treatment can halt disease progression in individuals with mild to moderate Alzheimer's. This non-invasive brain stimulation technique, already approved for conditions like depression, OCD, and migraines, is now being investigated for its potential to address cognitive decline associated with Alzheimer's.
How rTMS Targets Alzheimer's
rTMS involves using a magnetic coil to stimulate specific brain regions, aiming to reset dysfunctional brain activity patterns. Sinaptica's approach differs from previous attempts, such as Neuronix Ltd.'s NeuroAD, by targeting the precuneus, a brain region crucial for the default mode network involved in memory and cognition. In Alzheimer's disease, this area is often affected by beta-amyloid plaque buildup.
Ken Mariash, CEO of Sinaptica Therapeutics, explained, "We see very clear evidence that the nodes of the network are starting to disconnect, and that is highly correlated with Alzheimer’s progression." By stimulating the precuneus, rTMS seeks to activate neuroplasticity, enabling brain cells to form new connections and reinforce existing ones. The treatment is personalized using EEG to identify the optimal stimulation spot and dosage for each patient.
Phase 2 Trial Results
The Phase 2 trial involved 50 participants with mild to moderate Alzheimer's, randomized to either active rTMS or a sham treatment. Participants underwent a 45-minute calibration session, followed by 20-minute daily rTMS treatments for two weeks, and then weekly sessions for 22 weeks.
After 24 weeks, the active rTMS group showed no decline on an 18-point standardized dementia scale, while the sham group declined by 1.3 points. A separate study involving brain imaging of 16 participants revealed that the treatment also slowed brain shrinkage and improved the strength of the default mode network. Side effects were mild and temporary, including headache, skin discomfort, and neck stiffness.
Caveats and Future Directions
Despite the promising results, some experts urge caution in interpreting the findings. Mark George, a professor at the Medical University of South Carolina, noted potential methodological issues, such as incomplete blinding, and the small sample size from a single trial site. He cautioned against using terms like "breakthrough" or "unprecedented" to describe the results at this stage.
Sinaptica is currently designing a larger Phase 3 trial, incorporating Alzheimer's biomarker measurements, to further assess the effectiveness of rTMS. The company received a Breakthrough Device Designation from the FDA, which is designed to expedite the regulatory process for promising medical devices.
While the Phase 2 results are encouraging, further research is needed to confirm the efficacy and safety of rTMS as a treatment for Alzheimer's disease.
