Abstract Details

Title Feasibility, Safety, and Efficacy of Gamma Sensory Stimulation as a Novel Therapeutic Intervention for Alzheimer’s Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) N1 - Neuroscience in the Clinic: Neurobiology of Learning and Memory in 2022 (12:50 PM-1:05 PM)

Poster/Presentation
Number 001

Background

40Hz gamma sensory stimulation diminishes AD pathology, neurodegeneration, and brain atrophy, synaptic and learning dysfunctions in transgenic mice carrying AD-related human pathological genes (Adaikkan & Tsai, 2020). These results initiated the development and validation of non-invasive, gamma sensory stimulation as a potential therapeutic for AD treatment.

Objective

To evaluate the safety, tolerability, adherence, and efficacy of 40Hz sensory stimulation therapy in subjects with Alzheimer’s disease (AD).

Design/Methods

Participants on AD spectrum were randomized to receive daily, one-hour, EEG-calibrated, noninvasive audio-visual stimulation, or sham stimulation in a 6-month clinical trial (Overture trial; NCT03556280) using Cognito Therapeutics medical device. Both safety (MRI, physical and neurological exams), and efficacy (AD cognitive and functional instruments, volumetric MRI) were assessed.

Results

A total of 135 subjects were screened, 74 were randomized, and 53 completed the trial. The rate of AEs during the trial were roughly equivalent between groups. There were no unexpected serious treatment adverse events. Over the 6-month treatment period, changes in ADCS-ADL scores were significantly better in the treatment group compared to sham, indicating a 78% slowing in functional decline (P<0.0003). Similarly, the treatment group demonstrated a statistically significant 83% (p<0.013) reduction in cognitive decline, shown by changes in MMSE scores. The outcomes of MADCOMs, ADAS-cog14 and CDR-sb were not statistically different between groups. Quantitative MRI analysis revealed that whole brain volume loss in the treatment group demonstrated a significant, 72% reduction in brain atrophy (p<0.01) compared to sham group. Reduced lateral ventricle enlargement and diminished loss in cortical thickness in the occipital cortex have been also observed. MRI data demonstrated absence of ARIA in all subjects.

Conclusions

Long-term, daily, self-administered, home-use of gamma sensory stimulation is both safe and well tolerated in AD subjects. Patients given gamma stimulation therapy maintained cognitive and functional abilities. Gamma sensory stimulation reduced brain atrophy, indicating potential disease-modifying effects in AD.

Authors/Disclosures
Mihaly Hajos, PhD (Cognito Therapeutics) PRESENTER	Prof. Hajos has received personal compensation for serving as an employee of Cognito Therapeutics, Inc. Prof. Hajos has stock in Cognito Therapeuitcs. Prof. Hajos has stock in Biogen. Prof. Hajos has stock in Pfizer. Prof. Hajos has received intellectual property interests from a discovery or technology relating to health care.
Jonathan T. Megerian, MD, PhD (Childrens Hospital of Orange County Thompson Autism Center)	Dr. Megerian has received personal compensation for serving as an employee of Yamo Pharmaceuticals. Dr. Megerian has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cognito Therapeutics. Dr. Megerian has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kuzani Pharmaceuticals. Dr. Megerian has received research support from Childrens Hospital of Orange County.
Evan Hempel (Cognito Therapeutics)	No disclosure on file
Aylin Cimenser, PhD (Cognito Therapeutics, Inc)	Dr. Cimenser has received personal compensation for serving as an employee of Cognito Therapeutics, Inc. An immediate family member of Dr. Cimenser has received personal compensation for serving as an employee of Boston Scientific Corporation. Dr. Cimenser has stock in Cognito Therapeutics Inc. An immediate family member of Dr. Cimenser has stock in Boston Scientific Corporation. Dr. Cimenser has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Cimenser has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Cimenser has received publishing royalties from a publication relating to health care.
Alyssa Boasso (Cognito)	No disclosure on file
	No disclosure on file
Martin Williams	Martin Williams has received personal compensation for serving as an employee of Cognito Therapeutics. Martin Williams has received stock or an ownership interest from Cognito Therapeutics. Martin Williams has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
Suzanne Hendrix, PhD	Dr. Hendrix has received personal compensation for serving as an employee of Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Pentara Corporation. The institution of Dr. Hendrix has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pentara Corporation. Dr. Hendrix has stock in Pentara.
Brent Vaughan (Cognito Therapeutics, Inc.)	No disclosure on file
Zach Malchano (Cognito Therapeutics)	Mr. Malchano has received personal compensation for serving as an employee of Cognito Therapeutics, Inc.. Mr. Malchano has received stock or an ownership interest from Cognito Therapeutics.