Precision Neuromodulation Decreased Brain Atrophy and Increased Connectivity in Key Brain Network in Alzheimer’s Patients
July 09 2024 - 7:00AM
Business Wire
Study by Sinaptica scientific co-founders
published in Alzheimer's Research & Therapy
Imaging analysis revealed personalized rTMS-EEG
preserved structural integrity, enhanced functional connectivity,
and slowed atrophy in areas of the Default Mode Network, the
primary memory network impacted by Alzheimer’s that is targeted by
the therapy
Findings support the company’s Phase 2 data in
Mild/Moderate Alzheimer’s showing >80% disease slowing on
cognitive & functional endpoints
Sinaptica Therapeutics, Inc., a clinical-stage company leading
the development of a new class of personalized neuromodulation
therapeutics to treat Alzheimer’s (AD) and other neurodegenerative
diseases, today announced publication in the journal Alzheimer's
Research & Therapy of a study using MRI and fMRI neuroimaging
analysis to evaluate structural and connectivity changes in the
brains of patients with mild-to-moderate Alzheimer’s after
treatment using a proprietary non-invasive precision therapy. This
patented approach to personalized neuromodulation of the Default
Mode Network, based on rTMS-EEG technology, referred to as “nDMN”,
is being developed by Sinaptica.
The publication, titled “Macro and micro structural preservation
of grey matter integrity after 24 weeks of rTMS in Alzheimer’s
disease patients: a pilot study,” a sub-study of a larger
randomized Phase 2 trial, showed statistically significant slowing
in the rate of grey matter atrophy in the Precuneus, which is a key
node of the Default Mode Network (DMN), the primary brain network
impacted by Alzheimer’s disease. The DMN is critical for episodic
memory and one of the earliest brain regions to be correlated with
amyloid deposits, grey matter loss, and functional connectivity
disconnection.
In addition to preserving grey matter at the macro level,
detailed microimaging analysis, supported by an independent group,
Oxford Brain Diagnostics, also showed that the neuromodulation
treatment preserved microstructural integrity of the Precuneus, as
measured by AngleR, a proprietary measure of microcortical damage,
as well as across regions of the DMN, with high spatial
specificity.
Moreover, at a connectome level, treatment increased functional
connectivity in the Precuneus, and across the DMN as measured by
fMRI, but not in the unrelated areas of the brain such as the motor
cortex, pointing to the possibility that nDMN specifically
strengthens the target network responsible for memory.
“Brain atrophy is a direct result of Alzheimer’s disease, and
cognitive impairment directly correlates with both brain shrinkage
and diminished connections in the DMN,” said Giacomo Koch, MD, PhD,
Sinaptica scientific co-founder and primary author of the study.
“This is the first pilot study aimed at investigating the
neurobiological alterations reflected in structural and functional
changes after multiple sessions of personalized rTMS-EEG targeting
the DMN via the Precuneus in Alzheimer’s patients. The results
provide novel evidence supporting the idea that nDMN may be able to
slow down atrophy and increase functional network connections in
patients with Alzheimer’s disease.”
The research design included a subset of 16 patients from the
larger Phase 2 trial, evaluated with additional imaging studies.
The personalized nDMN treatment protocol consisted of two phases, a
daily “intensive” phase with 10 daily sessions delivered in the
first two weeks, and a weekly “maintenance” phase with 22 weekly
sessions delivered in the subsequent 22 weeks. At baseline and
after 24 weeks of treatment, participants underwent structural and
functional MRI measurements. The MRI and fMRI measurements were
analyzed at three different levels: macro-structural,
micro-structural, and functional connectivity changes.
“This imaging data supports the full Phase 2 clinical trial
results in Alzheimer’s patients that are the foundation of
Sinaptica, showing objective evidence that our non-invasive therapy
impacts the brain on multiple specific and biologically relevant
levels,” said Sinaptica CEO Ken Mariash. “It underscores the
capability of nDMN, when properly calibrated, to safely induce
plasticity, create new connections, slow atrophy, and prevent the
DMN from disconnecting, which is a hallmark of Alzheimer’s
disease.”
Sinaptica is building on positive data from the full nDMN Phase
2 study in Alzheimer’s, showing statistically-significant slowing
of clinical markers of disease progression was seen on the primary
endpoint, the Clinical Dementia Rating – Sum of Boxes (CDR-SB), and
on a key secondary endpoint, Alzheimer’s Activities of Daily Living
(ADCS-ADL)—both showing >80% disease slowing—along with two
other cognitive measures (ADAS-COG and MMSE) which also showed over
80% disease slowing at six months, as published by the company’s
scientific co-founders in the journal, Brain. The treatment was
well tolerated, and no serious adverse events were observed in
patients treated for six months. The company has also completed a
second Phase 2 study, with a 1-year endpoint, which will soon be
published in an upcoming issue of a peer-reviewed journal and
presented at CTAD in October. Sinaptica’s patented technology has
been granted FDA Breakthrough Device Designation, and the company
is preparing for a larger Phase 3 clinical trial in Alzheimer’s
patients at multiple sites.
About Sinaptica Therapeutics Sinaptica Therapeutics is a
clinical-stage neuromodulation therapeutics company leading the
development of a new class of personalized therapeutics to
revolutionize the treatment of Alzheimer’s and neurodegenerative
diseases. The company utilizes a patented non-invasive approach to
treating Alzheimer’s via precision neurostimulation of a key brain
network involved in memory, the Default Mode Network. This novel
approach slowed disease progression by >80% on all four
gold-standard cognitive and functional clinical endpoints in a
placebo-controlled Phase 2 clinical study, with results published
in the journal, Brain. The technology was granted Breakthrough
Device Designation by the FDA in 2022 and the company is preparing
for a pivotal randomized controlled clinical trial in 2025.
Sinaptica’s mission is to bring a safe, effective, and non-invasive
neuromodulation therapy to Alzheimer’s patients that can help to
significantly slow the progression of both cognitive and functional
decline. Learn more at sinapticatx.com and follow us on LinkedIn
and X @SinapticaTX.
The SinaptiStim™ System is for investigational use only. It has
not been approved by the U.S. Food and Drug Administration and is
not available for commercial sale in any geography.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240709586783/en/
Media: Kathryn Morris, BrightPoint
kathryn@brightpointny.com 914-204-6412