The Silicon Review
Identifying an accurate, convenient measure of stress is arguably one of the most challenging conundrums in medical diagnostics. Consequently, stress state, as possibly the most overlooked element of personalized medicine, has been considered a ‘soft’ science for decades, if not centuries. Without a precise measurement, its accepted and significant impact on disease remains imprecise and therapeutics to mitigate it speculative.
However, stress is controlled within the brain by the autonomic nervous system (ANS). It has two components constantly battling subconsciously for predominance: the ‘sympathetic’ (fight-or-flight) and the ‘parasympathetic’ (rest and recovery). With new technology, these components can be more accurately measured, analyzed, and reported in real time.
The Inmedix ANS Neuroscan™ collects around 350 heart beats on an ECG rhythm strip with a patient lying supine. That signal is sent via Bluetooth to an iPad, which then transmits it to the Azure cloud for storage and analysis with next-generation heart rate variability (HRV). The cloud then reports ANS values to the iPad for immediate decision making. This 5-minute ECG technique indirectly quantifies ANS state through the effect of stress on resting heart rhythm and has been broadly adopted for elite training by professional sports and US Special Forces.
Fundamentally, stress activates the immune system to enhance survival: a concept recently described as ‘immuno-autonomics’. However, stress also drives autoimmune disease to untreatable excess. ANS profile varies within individuals based on their genetics, life experiences, and recent activities. Surprisingly, high fight-or-flight stress state can be silent, analogous to hypertension. Inmedix has published how this ANS diagnostic may predict rheumatoid arthritis(RA) treatment outcome a year in advance, guide significantly improved treatment outcomes and substantially reduce cost of care.
Inmedix was founded in 2006, and is based in Normandy Park, WA, USA. The company identifies actionable diagnostic biomarkers from bloodless human electrical signals using the Azure cloud, thereby replacing the massive infrastructure and thousands of technicians required by traditional clinical labs. The Inmedix ANS Neuroscan™ point-of-service diagnostic is anticipated to be available in 2021 to rheumatologists and other clinicians interested in quantifying ANS stress.
In conversation with Andrew J. Holman, MD, Co-Founder and CEO of Inmedix
Q. What is the biology of stress?
Two systems work in coordination to manage endogenous (within the body) and exogenous (outside the body) stressors. The endocrine system with hormones (cortisol, etc.) responds over hours and days, while the autonomic nervous system (ANS) responds within milliseconds. The ANS is divided loosely into the parasympathetic (rest and recovery) and the sympathetic (fight-or-flight, adrenaline) components. Both elements balance each other, yet also compete for predominance, depending on bodily needs (survival or recovery). While the central brain controls ANS activity, it messages the rest of the body through the vagus nerve (parasympathetic) and spinal ganglia, leading to a delicate web-like network of nerves extending throughout the body (sympathetic). Essentially, the ANS manages all housekeeping functions, including breathing, pulse, blood pressure, temperature, digestion, and, more recently appreciated, the immune system.
Q. How does the ANS impact immune function?
In 2000, authors from the USA National Institutes of Health (NIH) introduced how the ANS impacted the immune system, including regulation of cytotoxic T-cell maturation and distribution, antibody production, cell migration and perhaps most fundamental, how ANS stress triggers the pro-inflammatory messenger molecules (cytokines) that coordinate nearly all immune activity. And, for every ‘on switch’ within biological systems, there must be a counterbalancing ‘off switch’. In 2002, Tracey described the Cholinergic Anti-inflammatory Reflex: how the opposite of fight-or-flight sympathetic stress - the parasympathetic vagus nerve - turned off inflammation when it was no longer needed to fight infections, etc.
Q. Are there new immuno-autonomic therapeutics?
It is important to remember that no immuno-autonomic treatments are approved by the FDA yet. However, parasympathetic activation through vagus nerve stimulation (SetPoint Medical) has significantly reduced RA activity and levels of pro-inflammatory cytokines (IL-1, IL-6, and TNFα). Generic oral medications (Inmedix) and treatment of co-morbid obstructive sleep apnea (a well-studied hyper-sympathetic state causing heart disease) also reduced RA activity through presumed immuno-autonomic mechanisms. Given how universally stress impacts disease, it is anticipated that most pharmaceutical companies will eventually pursue ANS state optimizing therapeutics to reduce how stress is responsible for driving so many diseases to untreatable excess.
Q. What are the prominent Inmedix achievements of Inmedix?
In 2007, Inmedix sold its first patent portfolio to Boehringer-Ingelheim pharmaceuticals for $10 MM after four studies, including two innovative randomized controlled trials validating how dopamine agonists for Parkinson’s disease reduced pain in patients with fibromyalgia. In 2008, Inmedix reported next-generation HRV as the first and only predictor of 52-week biologic treatment outcome in RA. In 2015, Inmedix reported enhancing biologic treatment remission in RA from 27% to 79% with generic medications. In 2019, University of Washington health economists independently projected Inmedix immuno-autonomic diagnostic and therapeutic strategies to reduce RA care’s US cost by as much as $34 billion over ten years. In 2020, Inmedix is creating a bloodless, cloud-based clinical laboratory to transform the bedrock of medical practice: diagnostics.
Q. What are the future plans for Inmedix?
The Inmedix ANS Neuroscan™ point-of-service diagnostic is anticipated to be available in 2021 to rheumatologists and other clinicians interested in quantifying ANS stress. Within five years, Inmedix expects a seismic shift as the practice of medicine will be transformed by providing reimbursed bloodless diagnostics utilizing the Inmedix digital diagnostic device to improve care, reduce healthcare costs and identify new ANS optimizing therapeutics, leveraging its proprietary cloud data. Today, clinicians treat only the disease. Tomorrow, they will comprehensively treat the individual by addressing adverse ANS profiles in parallel to treating disease. Inmedix seeks to ensure superior patient outcomes from current treatments as well as harness the power of prevention through targeted management of biological stress.
Meet the leader behind the success of Inmedix
Andrew J. Holman, MD has discovered and validated innovative solutions for some of the most challenging unmet clinical needs, including pain, fight-or-flight stress and immunology. As a Seattle rheumatologist, he specialized in autoimmune disease, fibromyalgia and hypermobility syndrome treatment and research for 25 years. Dr. Holman Co-Founded Inmedix to hold his patents and is widely published in peer-reviewed medical journals. He has often presented internationally as a guest lecturer and is a Clinical Associate Professor of Medicine at the University of Washington.