It’s not just about plaques: rTMS also reduces cognitive and functional decline in Alzheimer’s

The growing number of drugs gaining U.S. FDA approval for Alzheimer’s disease has kept their ability to reduce amyloid beta and tau proteins in the news, but the degenerative disease is not simply a matter of tangles and deposits. A loss of synaptic plasticity and disrupted neural networks underlie the signature impairment of memory and cognition – and those, researchers showed in a recent study in Brain, can be strengthened by non-invasive stimulation that addresses the brain’s electrical dysfunction.

“The brain is very much an electrical organ,” Sinaptica Therapeutics Inc. CEO Ken Mariash told BioWorld.

Sinaptica is banking on being able to manipulate the brain’s electrical signals to preserve its health and full capabilities. And, based on the Brain results, it appears to be more effective than drugs in achieving that aim.

The study showed an astonishing 82% slowing of Alzheimer’s progression in treated patients vs. controls and an actual improvement in activities of daily living over a six-month period.

The remarkable effectiveness did not surprise the neuroscientists at the Cambridge, Mass.-based company. “We are starting to look at pretty much every neurological disease as a network dysfunction,” Mariash said. “When you use a drug, you hope that the drug does the job by going through the bloodstream, through the blood-brain barrier and up into the appropriate region, but it will affect
nearly every region of the brain, it will not be specific to a specific network operation. With brain stimulation, you can go directly to the source of the problem and affect the network that you want to modulate.”

“We can induce specific activity at specific frequencies with our intervention and so bypass all those issues and you start to restore activity directly,” added Emiliano Santarnecchi, co-founder of Sinaptica, associate professor of Radiology, Harvard Medical School; director, Precision Neuroscience & Neuromodulation program and director, Network Control Laboratory at the Gordon Center for Medical Imaging at Massachusetts General Hospital in Boston.

Studies going back to the 90s showed that transcranial magnetic stimulation (TMS) induced plasticity in the brain and demonstrated that plasticity is the key mechanism of memory, Santarnecchi noted.

Individualized, precise stimulation is key

Sinaptica uses repetitive TMS (rTMS) to target the part of the brain it believes to be most affected by Alzheimer’s early in the disease, the precuneus region. To that technology, which is FDA approved for depression and obsessive-compulsive disorders, the company added neuronavigation.

“That means we can come within millimeter precision every time, reproducibly to exactly the same spot,” Mariash said. “The real estate in the brain is very dense. If you’re off by even a few millimeters, you cannot get the desired effect or even worse, you could induce off-target effects.”

The neuronavigation, originally designed for brain surgery, also enables the team to see exactly what is happening in the brain by marking where the brain is stimulated on a 3D map of the brain made from the patient’s brain MRI. The navigation enables “pulse-by-pulse adjustment of the stimulation, and we see a tremendous improvement in results and also the reliability of the intervention,” Santarnecchi told BioWorld.

“Every patient’s brain responds uniquely to TMS, and we know that because we look at the TMS EEG signals. We fire once to the precuneus and we listen to the reverberations around the network using 64-channel EEG, and we can see the propagation throughout the network of those signals. It forms a fingerprint pattern unique to every patient, so we calibrate the therapy based on the responses that we see in the network to make sure we get the right resonance and engagement of the default mode network.”

More than 80% slowing across all measures

The phase II Brain study included 50 patients with mild to moderate Alzheimer’s disease, assigned on a 1:1 ratio to precuneus stimulation with rTMS or a sham treatment over a 24-week period. Patients with precuneus stimulation maintained stable performance on the primary endpoint, the Clinical Dementia Rating Scale-Sum of Boxes score and had significantly better performances on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination and Alzheimer’s Disease cooperative Study-Activities of Daily Living (ADL) scale. They also demonstrated an enhancement of local gamma oscillations. In contrast, the sham group showed deterioration across all measures.

Overall, the treated group showed a more than 80% slowing of dementia progression across all endpoints.

“The primary endpoint was deliberately chosen to be on par with those pharmacological therapies. We designed the phase II to really put us in the same category of efficacy as those major drug trials,” Mariash noted. “And they didn’t progress at all in six months, which is really remarkable, where the sham group did progress quite a lot. The separation was over eight points on the ADL scale.”

Notably, the trial included patients with moderate dementia. “The drugs today are more focused on mild cognitive impairment and mild dementia patients. We think that’s because every drug that’s gone after mild to moderate patients has failed. It’s commonly accepted that [moderate] patients are very difficult to arrest the disease progression once they’re in that decline,” Mariash said. “So that made the finding even more remarkable showing 82% disease slowing in a really hard to treat patient population.”

Download full PDF here

SHARE THIS POST

Yohannes Iyassu

Software Consultant

Yohannes Iyassu is a seasoned executive in neuromodulation with over 15 years of experience specializing in implantable medical systems. He has a proven track record of developing and receiving regulatory approvals (PMA/IDE/FDA and CE Mark) for Spinal Cord, Sacral Nerve, and Deep Brain Stimulation therapies. In his role as a VP and Executive Director, Dr. Iyassu has effectively led multidisciplinary teams spanning systems, usability, electrical, software, mechanical, verification & validation, quality assurance, labeling, and manufacturing engineering.

Dr. Iyassu holds over 30 granted patents and earned a BS and MS in Electrical Engineering from the University of Denver. He received his Ph.D. in Electrical and Computer Engineering from the University of Massachusetts, Lowell specializing in Signal Processing, Distributed Systems, and Machine Learning.

Giovanni Frisoni, MD

Giovanni Frisoni, MD, is a clinical neurologist, Full Professor of Clinical Neuroscience at the University of Geneva, Switzerland, and Director of the Memory Clinic at Geneva University Hospital where he is leading a team of 40 clinicians and scientists. Formerly the Director at the National Alzheimer’s Centre in Bresca, Italy, Prof. Frisoni is author of about 700 scientific papers listed in PubMed, imaging editor for Neurobiology of Aging, and founding editorial board member of The Lancet Neurology.

He has led national and international projects funded by the European Commission, the Alzheimer’s Association, Italian and Swiss Ministries of Health, and industry. He is currently a leading figure worldwide in microbiota studies in dementia, has taken active part in the IWG initiative for the definition of global diagnostic criteria for Alzheimer’s disease, and is leading a European working group of experts tasked with developing protocols and procedures for the memory clinics of the future (brain health services for dementia prevention). Dr. Frisoni is an honorary member of the Austrian Neurological Society and the French Society of Neurology, and he received the Investigator Award Winner from the European Academy of Neurology in 2016.

Simone Rossi, MD, PhD

Simone Rossi MD, PhD is a Professor of Human Physiology. He is also a Neurologist and Neurophysiologist, currently leading the Brain Investigation & Neuromodulation Lab (Si-BIN Lab) at the Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Unit, University of Siena, where he also leads the Parkinson’s disease clinical activity.

Dr. Rossi is an international leader in the field of noninvasive brain stimulation, where his contributions include: technical developments (one patent for a new sham coil for TMS); use and developments of noninvasive brain stimulation techniques (TMS, tDCS, tACS) as neuroimaging procedures in cognitive neuroscience, with a focus on memory, therapeutic neuromodulatory tools in neuropsychiatry, and neuroehnancement (including ethical issues); individuation of neurophysiological markers of psychiatric diseases; noninvasive investigation of neural plasticity mechanisms and brain connectivity, studied with EEG, TMS-EEG combination and rsFMRI. He also helps in the development of wearable robotic devices (in collaboration with Prof. Domenico Prattichizzo) to improve human health, for stroke people, Parkinson’s disease patients and tinnitus sufferers (three patents).

Dr. Rossi has authored 183 full text publications on peer-reviewed scientific journals indexed by Current Contents-Life Science (and 11 chapters in books), with an overall Impact Factor of about 804 (mean per publication: 4.2), H-index: 58. He has more than 17900 citations.

Dr. Rossi received his M.D. in 1987 at the University of Firenze, his specialization in Neurophysiopathlogy in 1990 at the University of Genova, and a second specialization in Neurology in 1999 at the University of Siena; in 1996, he obtained the PhD in “Pathophysiology of Nervous Functions”. He has been trained in neurology and neurophysiology in Siena, in Roma, under the supervision of Prof. Paolo Rossini and in Germany (Ulm, Freiburg).

He is or has been a member of the Editorial Boards of Behavioural Neurology, Brain Stimulation, ISNR Neurology, and Clinical Neurophysiology and is past President of the Italian Society of Psychophysiology & Cognitive Neuroscience. Currently, he is secretary of the Italian Society of Clinical Neurophysiology. He is also an occasional reviewer of 98 international scientific journals in neurology, neurophysiology, psychiatry and neuroscience areas (including Nature Reviews Neurology, Lancet Neurology, Neurology, Annals of Neurology, Journal of Neuroscience, Trends in Cognitive Sciences, Current Biology, Biological Psychiatry, American Journal of Psychiatry, Elife, etc.).

Dr. Rossi is Referee for the European Research Council, for the Medical Research Council (MRC) UK, for The French National Research Agency (ANR), for the Netherlands Organisation for Scientific Research, for the Israeli Scientific Foundation, for the Weston Brain Institute. He is a reviewer of the Italian Ministry of Research for the evaluation of scientific production of Italian Universities.
Dr. Rossi is or has been granted as Unit Leader in many Italian research projects and is responsible for the local neuroscientifc aspects in two European granted projects in Robotics.
Dr. Rossi is a Consultant for EBNeuro and for Neurocare Group Italy.

Lorenzo Di Gioacchino

Board Member

At F2i since 2008, he is a Partner and Head of the Legal Area. He provides assistance in the investment and divestment of the equity investments held by the Funds managed by F2i, in the legal aspects of the new Funds’ fund-raising activity, and provides general support to the company’s various departments.

Prior to joining F2i, he worked for four years at the Grande Stevens law firm, where he dealt with corporate, commercial and financial market law matters, with a focus on mergers and acquisitions. Previously he worked at the law firm Pavia and Ansaldo, also in the field of commercial and corporate law and he has been visiting lawyer at the London offices of law firm Weil, Gotshal & Manges and at London-based law firm Herbert Smith.

He serves on the Board of Directors of EI Towers and Sagat.

He graduated in Law from La Sapienza University, Rome.

Dinesh Moorjani

Board Observer

Dinesh Moorjani is a serial tech founder & CEO, venture capital investor, and adjunct professor. Dinesh was the Founder and CEO of Hatch Labs Inc., where he cofounded numerous software companies from ground up, including Tinder (NASDAQ: MTCH). Dinesh started several other software businesses, including Saffronart – a global eCommerce marketplace for Indian fine art and collectibles, backed by Sequoia Capital. He cofounded Kleverbeast, a no-code SaaS application development platform, and Monet Analytics, an AI SaaS business that decodes human emotion.

Dinesh served in numerous executive leadership roles at multinational corporations, including as Managing Director at Comcast Ventures, Sr. Vice President and Group Head of Mobility at IAC/InterActive Corp, and in various leadership roles at Samsung Electronics in the US and Asia. He built his early career in the Global Energy Practice at AD Little, Goldman Sachs, and as an early employee at Mainspring (IPO 2000, acquired by IBM 2001). Dinesh served as an independent board director at Alight (NYSE: ALIT) and on the advisory boards of Fortune 500 companies including American Express, Assurant, and Cox Automotive. He held the board observer seat at Zoox (acquired by Amazon), a leader in autonomous vehicles. Dinesh served as an advisor to Warburg Pincus, the global private equity firm, where he was previously an EIR sitting on company boards and co-investing alongside the firm.

Dinesh is a faculty advisor and senior lecturer at the UCLA Anderson School of Management, and guest lectures at Harvard, Stanford, and MIT. He serves on the Harvard Business School California Research Center Advisory Board. Dinesh supports disenfranchised youth and education through his non-profit work as a board director at the United Friends of the Children and the Organization for Social Media Safety. He also serves as a board trustee at the University of California, Merced. Dinesh earned his B.S. in Chemical Engineering from Northwestern University and MBA from Harvard. He is currently a Stanford University engineering doctoral student focused on climate innovation and sustainable finance.

Caitlin

Scientific Advisor

Dr. Ana Pereira completed her neurology residency at Harvard University, with sub-specialty trainings in Cognitive Neurology at Columbia University, Post-Doctoral Research Fellowship at Columbia University and Translational and Clinical Investigation at Rockefeller University in New York City where she was an Assistant Professor of Clinical Investigation before moving to Mount Sinai. Clinically, Dr. Pereira evaluates patients at the Barbara and Maurice Deane Center for Wellness and Cognitive Health at The Mount Sinai Hospital, having expertise in diagnosing and treating neurodegenerative disorders and other cognitive syndromes.     Dr. Pereira’s research focuses on furthering knowledge of the neurobiology of aging and Alzheimer’s disease, taking into account the selective vulnerability of glutamatergic neural circuits to synaptic changes in aging and neuronal loss in Alzheimer’s disease. She seeks to explore mechanisms underlying these susceptibilities along with effective therapeutic interventions. 

Ana Pereira, MD

Ana Pereira completed her neurology residency at Harvard University, with sub-specialty trainings in Cognitive Neurology at Columbia University, Post-Doctoral Research Fellowship at Columbia University and Translational and Clinical Investigation at Rockefeller University in New York City where she was an Assistant Professor of Clinical Investigation before moving to Mount Sinai. Clinically, Dr. Pereira evaluates patients at the Barbara and Maurice Deane Center for Wellness and Cognitive Health at The Mount Sinai Hospital, having expertise in diagnosing and treating neurodegenerative disorders and other cognitive syndromes. Dr. Pereira’s research focuses on furthering knowledge of the neurobiology of aging and Alzheimer’s disease, taking into account the selective vulnerability of glutamatergic neural circuits to synaptic changes in aging and neuronal loss in Alzheimer’s disease. She seeks to explore mechanisms underlying these susceptibilities along with effective therapeutic interventions.

Lisa Fosdick

Acting VP of Clinical

Lisa brings a decade of experience in neuromodulation for Alzheimer’s Disease (AD) guiding Functional Neuromodulation (deep brain stimulation of the fornix for AD) through two FDA trials and obtaining CE mark.  Prior to that her medical device experience spanned 7 years as Director of Data Management with NAMSA and Director of Clinical and Biostatistics at CVRx.  Earlier work included driving the creation of an HIV trials network spanning 23 countries with 4 regional coordinating centers to conduct several pharma-driven trials. Lisa has a Masters of Science in Biostatistics from the University of Minnesota. 

Casey Lynch, MS

Casey Lynch has more than 25 years of experience as an entrepreneur, executive and director with a focus on development of treatments for neurological disorders. She is currently the CEO of Lighthouse Pharmaceuticals and Managing Partner of Sonoma Bioventures, an investment and advisory firm. She has been a member of the board of directors of Longboard Pharmaceuticals (LBPH), a public company developing the next wave of neuropharmaceuticals, since February 2021 and a member of the review board of the Alzheimer’s Drug Development Foundation since September 2022. She previously co-founded and served as President and Chief Executive Officer and member of the board of directors of Cortexyme, Inc., a public biotechnology company, from July 2014 through January 2022, and as Chairman of Cortexyme’s Board of Directors from November 2018 through January 2022. She was a member of the board of directors of the California Life Science Association, a trade association representing California’s life science industry, from 2019 to 2021. Prior to co-founding Cortexyme, Ms. Lynch co-founded various companies and organizations in the biotechnology industry including Aspira Biosystems, an artificial antibody platform and NeuroInsights, an information, event and advisory firm focused on the intersection of neuropharma, neurodevices and neurodiagnostics. Ms. Lynch holds a B.S. in Neuroscience from the University of California, Los Angeles, and an M.S. in Neuroscience from the University of California, San Francisco.

Anthony Arnold

Anthony Arnold, Strategic Advisor, is the President & CEO of Sensydia Corporation; a leader in the field of artificial intelligence based, non-invasive cardiac assessment. Anthony is also CEO & Founder of the boutique medtech consulting firm, Precys. Before being named CEO for Sensydia, Anthony spent eight years leading SetPoint Medical; a pioneer in the field of bioelectronic medicine dedicated to treating patients with debilitating inflammatory diseases. Arnold led the company and built a world-class team that delivered a revolutionary micro-implantable platform, novel therapeutic pathway and successful human trials in Europe and the US.

Anthony brings more than 20 years of experience in the development and commercialization of high-technology medical devices. Prior to SetPoint, Anthony served as Vice President of Marketing for Boston Scientific. Anthony was also Director of Marketing at Medtronic, responsible for the launch and explosive growth of the StealthStation navigation system. Prior to Medtronic, Anthony held a variety of positions of increasing responsibility in marketing and R&D with Smith+Nephew.

Jeffrey L. Cummings, MD ScD (HC)

Jeffrey L. Cummings joined the UNLV School of Integrated Health Sciences in 2019 as research professor within the department of brain health. Dr. Cummings is the Joy Chambers-Grundy Professor of Brain Science, an endowed professorship. He is the Director of the Chambers-Grundy Center for Transformative Neuroscience, a center devoted to using the tools of neuroscience and neurologic drug development to transform people’s lives.

Prior to UNLV, Dr. Cummings served as founding director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, and as director of the Mary S. Easton Center for Alzheimer’s Disease Research, and director of the Deane F. Johnson Center for Neurotherapeutics, both at UCLA.

A world-renowned Alzheimer’s researcher and leader of clinical trials, Dr. Cummings has been recognized for his scientific and leadership contributions with the American Geriatrics Society’s Henderson Award (2006), the national Alzheimer’s Association’s Ronald and Nancy Reagan Research Award (2008), and the American Association of Geriatric Psychiatry’s Distinguished Scientist Award (2010). Dr. Cummings’ interests embrace clinical trials, developing new therapies for brain diseases, and the interface of neuroscience and society. Dr. Cummings has published nearly 800 articles and 44 books devoted to neuroscience, Alzheimer’s disease, and clinical trials.

Dr. Cummings received the Society for Behavioral and Cognitive Neurology’s Lifetime Achievement Award (2017), the International Society of CNS Drug Development’s Leadership and Achievement Award and the national Alzheimer’s Association’s Bengt Winblad Lifetime Achievement Award (2018). Additionally, he was featured in Gentleman’s Quarterly (June 2009) as a “Rock Star of Science.™”

Henry Peck

Henry Peck, Digital Biomarker Advisor, is the Vice President of Growth & Strategy at LSI (Life Science Intelligence™), an ecosystem of software, services, and events that enables thousands of medtech leaders around the world access the intelligence and relationships needed to build breakthrough businesses. Henry’s role spans both the company’s global partnering events, who’s emerging company alumni raised over $1.45 Billion in capital in 2022, and its Medtech Market Intelligence business, which is a trusted partner for syndicated and custom research and data solutions to the largest Medtech, Life Science, and Professional Services organizations, from Medtronic to McKinsey & Co.

Prior to his current role, Henry was the Director of Strategy and Marketing at Altoida, a precision neurology company pioneering novel digital cognitive assessment and diagnostics with augmented reality and machine learning. As one of the first team members beyond the founding scientific team, Henry was integral in winning FDA Breakthrough Device Designation for the technology’s prognostic and diagnostic application in Alzheimer’s disease, establishing partnerships and multi-million dollar commercial deals with global pharmaceutical companies and digital therapeutics providers, and securing bridge financing from new and existing investors including Whitecap Venture Partners, M Ventures (Merck KGaA), Hikma Ventures, HonorHealth, and more.
Henry began his career in robotics, primarily with Auris Health (Johnson & Johnson) where he supported upstream strategic marketing and portfolio management for a novel suite of robotically-driven stapling and advanced energy devices leveraging Ethicon’s portfolio of laparoscopic surgical devices (ECHELON™, ENSEAL™, HARMONIC). An engineer by trade, Henry holds a BS in Mechanical Engineering from Carnegie Mellon University and has conducted research in upper-limb extremity prosthesis and human performance augmentation via CMU’s Human-Computer Interaction Institute and Robotics Institute.

Alessio Travaglia

Alessio Travaglia is a neuroscientist with over 15 years of experience in basic and translational neuroscience, in academia, non-profit, management consulting, and venture philanthropy.

Currently, he works as the Director, Neuroscience at the Foundation for the National Institutes of Health (FNIH). In this role, he leads the Neuroscience programs, facilitate the advancement and execution of innovative Public-Private Partnerships, engage international participation from government, industry, academia, patient-advocacy and private sector organizations.

Jim Schwoebel

Jim Schwoebel, SW/ML Advisor, is an Engineering Manager @ Verily building out Verily Workbench (formerly Terra), a scalable, secure research platform to help biomedical researchers accelerate scientific discoveries. He has over 10 years of experience building startups and R&D partnerships in the areas of machine learning, digital health, and software engineering. Prior to joining Verily, Jim was the CEO of NeuroLex Laboratories, a company focused on using voice as a marker for early diagnosis of psychiatric and neurological diseases. Before being acquired by Sonde Health, NeuroLex had key partnerships in biopharma, grew its data bank to over 500,000 voice files and expanded its core SurveyLex product to thousands of users. Jim received his BS in Biomedical Engineering from Georgia Tech.

Emiliano Santarnecchi PhD, PhD

Scientific Co-Founder

Emiliano Santarnecchi is an Associate Professor of Radiology at Harvard Medical School (HMS), and the director of the Precision Neuroscience & Neuromodulation program (PNN) and the Network Control Laboratory at the Gordon Center for Medical Imaging at Massachusetts General Hospital (MGH).

Dr. Santarnecchi’s program focuses on combining multimodal neuroimaging (e.g., MRI, fMRI, DTI, PET) and electrophysiology (e.g., EEG, EMG, MEG) methods for the identification of novel biomarkers and the development of therapeutic approaches for patients with neurological and psychiatric conditions.

In particular, Dr. Santarnecchi’s research is centered around the development of personalized, network-based Noninvasive Brain Stimulation (NiBS) approaches to modulate brain plasticity, guide connectome rewiring and enhance cognitive function, with the ultimate goal of promoting Brain Health and healthy Aging. His team is currently working on machine learning and AI-based solutions for perturbation-based brain connectivity analysis (TMS-EEG, fMRI), NIBS approaches to modulate sleep and memory, high-frequency transcranial electrical stimulation interventions for the treatment of Alzheimer’s disease and Frontotemporal dementia, and novel fMRI markers of disease progression in patients with brain tumors.

Giacomo Koch MD, PhD

Scientific Co-Founder

Giacomo Koch, MD. PHD is a neurologist and neuroscientist. He is Full Professor of Human Physiology at University of Ferrara and leads the non-invasive cortical stimulation lab at Santa Lucia Foundation in Rome, Italy.

Prof. Koch has a world-class experience in the field of clinical neurophysiology. His main expertise is in the application of non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), mainly used in combination with structural and functional magnetic resonance imaging (MRI) and with electroencephalography (EEG).

The main goals of his research are to understand the mechanisms underlying cortical plasticity and cortical connectivity in the healthy human brain, to develop novel therapeutic approaches to promote recovery of neurological functions trough methods of non-invasive brain stimulation. He pioneered novel research based on multifocal TMS to investigate in real-time the activation of cortical circuits and to study the mechanisms of cortico-cortical plasticity. Prof. Koch performed several clinical trials evaluating the therapeutic efficacy of rTMS in neurological disorders such as Parkinson’s disease and stroke.

The main current focus of his research is on the field of Alzheimer’s disease (AD) and dementia. Prof. Koch conducted a series of clinical studies that led to the first clinical evidence that therapy with dopaminergic agonists such as rotigotine, may slow cognitive decline and preserve functional activities in patients with AD.  The translational approach of his research has been directed in the past 10 years to find novel therapies for AD that are based on personalized non-invasive brain stimulation therapies.

He is the author of >320 peer-reviewed publications and several book chapters. H index: 65 (Scopus).

Greg Harper

Acting VP of R&D

Mr. Harper has a proven track record in program management and leading global teams across all phases of the product development lifecycle -    from ideation & feasibility, through design & development, production ramp-up, installed base maintenance, and end-of-life.   

He has held leadership roles in Neuronetics, Philips Medical Imaging, GE Appliances, GE Medical, and GE Aerospace. Mr. Harper has directed global teams in the US, France, Israel, India, and China with a focus on talent development, and creating a culture of innovation, functional excellence, and process controls.    Mr. Harper holds a BS in Electrical Engineering from Valparaiso University, and an MBA from the University of Wisconsin.

Chris Thatcher

Chris Thatcher is a senior life sciences executive experienced as a board member, CEO and Divisional President in the commercialization of Class I, II, and III medical devices, for public or privately owned companies, with capital equipment, disposables, implantable or service agreements utilized in the operating room or office based, domestically and internationally. He has expertise in enterprises ranging from $20M to $425M in annual revenues, converting debt, venture funding or Initial Public Offering proceeds into successful turnarounds by accelerate revenue growth, margin expansion, operating leverage and ultimately EBITDA for their respective enterprises.

Ken Mariash

CEO

As CEO of Sinaptica, Ken is leading the team to advance the company’s personalized precision neuromodulation therapy for Alzheimer’s.

Prior to Sinaptica, Ken has 20+ years leading and growing new business ventures on both the ‘Buy Side’ and the ‘Build Side.’

He started his career in management consulting at Charles River Associates, then jumped to industry at CSL, then Baxter BioScience (now Takeda), and Boston Scientific, with leadership roles in marketing, strategy, and corporate development. At Boston Scientific’s nearly $1B Neuromodulation division, he was the global commercial lead for the highly successful Cosman RF ablation business he helped acquire.

He also built the division’s Strategy function, providing leadership in areas including strategic planning, BD assessment, R&D portfolio management, digital strategy, and investments in next-gen platforms & new indications. In 2019 he joined EBT Medical, a venture-backed, clinical-stage startup developing a disruptive neuromodulation device for overactive bladder, where he oversaw all commercial aspects.

Rich Macary

President

Rich Macary is the President of Sinaptica Therapeutics, a clinical-stage electromagnetic therapeutics company developing a novel, noninvasive closed loop neuromodulation approach for the treatment of Alzheimer’s disease.  As one of the company’s co-founders, Rich helped drive product development and partnering efforts as well as securing FDA Breakthrough Device Designation for the company’s proprietary SinaptiStimTM- AD System.  Prior to his current role, Rich was a consultant, strategic advisor and a senior executive at Sarepta Therapeutics, a global biotechnology company and leader in RNA based therapeutics and genetic medicines targeting rare diseases. In his role as Vice President of Business Development, Rich focused on developing new opportunities and therapeutic targets for the company’s RNA technologies as well as complimentary technologies and related IP.  Prior to and post his roles at Sarepta, Rich held several senior executive roles at Delos, a wellness real estate and technology company, where he lead business development, strategic investments and overall strategy as both President of Delos Ventures and Chief Strategy Officer.  In his roles at Delos, Rich achieved a number of key accomplishments including conceiving, developing and launching the Well Living Lab, a Delos and Mayo Clinic collaboration to study the impact of indoor environments on the health and well-being of building occupants. Rich spent the prior 15  years as a corporate consultant, advisor and analyst to both institutional and high-net-worth investors as well as a consultant, advisor, investor and board member to several public and private early to mid-stage companies operating in a diverse range of industries including biotechnology, medical devices, software, fintech and consumer products among others. Rich currently holds several board positions and remains a managing partner of Macary Advisors, a biotech/medtech consulting and advisory firm currently engaged with several promising companies within the fields of diagnostics, therapeutics, medical devices and digital health.  His research and opinions have appeared in many media outlets including Forbes, The Wall Street Journal, Wired, CNN, Barron’s, Reuters and Bloomberg.