You may know the term “digital therapeutics,” but how about the specialized category of “digital neuro-therapeutics”? MindMaze, which has developed a platform approach to creating prescription digital therapeutics for neurological diseases like stroke, Alzheimer’s, and Parkinson’s has just landed $105 million in fresh funding from Concord Health Partners to further advance development of this unique category of pDTx’s.
CEO Tej Tadi, CFO Kevin Gallagher, and Chief Medical Director John Krakauer get us smart on the neuroscience behind MindMaze, their device-plus-gaming interventions, and how they are gaining reimbursement for their brain health and recovery therapies. Each therapeutic is a bit different – MindPod Dolphin, for example, helps patients rehab upper limb motor skills by way of a dolphin-themed gaming experience that incorporates sensors and an anti-gravity vest. The team says there are 10 clinical trials underway across seven indications, with the goal to bring at least three new prescription digital therapeutics to market by next year.
How will this new funding – and a partnership with the American Hospital Association – aid US market expansion for Swiss-based MindMaze? We explore the company’s growth plans, talk about market readiness for digital therapeutics, and even find out the backstory behind how Leonardo DiCaprio ended up on their cap table.
A 35-year-old woman complains of weakness of the right side of her face and pain behind the right ear. She lives in an urban environment and denies any recent illnesses. She is not vaccinated against COVID-19 but is COVID negative.
What do you think, I was asked at our Morning Report? Well, I said, it sounds like a straightforward Bell palsy. The pain around the ear suggests swelling of the VIIth cranial nerve in the facial canal and the stylomastoid foramen, a very common historical point, I opined; so much so that its absence would make me doubt the diagnosis and make me consider other causes of facial palsy such as sarcoidosis or Borreliosis, though the urban environment argues against that tick born disease. Then we went around the room, expanding the differential diagnosis (as this exercise is often called) to include tumors of the parotid gland, leptomeningeal metastases and many more. At one minute before the end of the thirty- minute conference, a photo of the patient was shown. There was only one problem. There was no facial weakness, but rather she had a definite Horner syndrome on the right with a smaller pupil and subtle ptosis due to weakness of the Muller muscle, a small circular sympathetically innervated muscle that acts as a minor controller of the palpebral fissure. The patient’s pupils were not tested in bright and then dim light, nor was sweating tested because why would one do those things in someone with facial weakness and pain around the ear. In fact, this patient had nothing like a Bell palsy but rather Raeder syndrome, a painful oculosympathetic (Horner) syndrome, which implicates a disease of the carotid artery. Once this was discovered it was learned that the patient had hyperextensibility of the joints and hadn’t suffered any neck trauma. Now a spontaneous dissection of the right carotid artery becomes the focus of thought with a very different implication for therapy and prognosis.
This experience vividly emphasizes two traps in the diagnostic process: thinking fast and framing. As Daniel Kahneman and the late Amos Tversky have articulated and summarized in their book, ThinkingFast and Slow, there are two subsystems within the nervous system that they dubbed system one and system two. System one is a very rapidly acting, involuntary system which estimates the likelihood of a given circumstance and reacts to it. System two is a voluntary, tedious, slow system that weighs evidence, considers the frequency of a likelihood in the environment according to The Reverend Bayes’s prior probability. In neurology, system one is the autonomic nervous system (or the reptilian brain as it was called by the late Paul MacLean in his triune brain). System two is the cerebral cortex with its complex networks that facilitate various aspects of awareness, an aspect of consciousness. Neither system is good nor bad, as both have their place. The first presumably survived the rigors of evolution because it allowed our ancestors to react to potential threats rapidly (i.e. a movement in peripheral vision is not analyzed; it is rather escaped as if it were a snake, even though Bayesian reasoning would predict that it was probably a stick). System two allows for more accurate conclusions in less time sensitive circumstances. What happened to me in the conference was that my system one rapidly generated a theory, but this was based on incorrect data (it was a snake; not a stick). If a mistake is made early in the diagnostic process, the processes thereafter are all distorted and there is virtually no way to reach the correct answer. Recall Conrad Waddington’s epigenetic landscape, wherein he used a metaphor (marbles rolling down a hill) to describe how mistakes early in a developmental process have enormous effects on the ultimate outcome, whereas errors later in the process are less destructive. In addition to my system one error, I was also taken in by the framing shortcut (heuristic). The person who presented the case had a theory of his own, which was promulgated in the headline: a woman with a painful facial palsy. In fact, it was a woman with a painful Horner syndrome. The moral of the story is that I should have looked at the photograph first. That would have avoided the futile task of elaborating an expanded differential diagnosis which, after all, is a nothing but a list of wrong answers followed by the right answer.
Awareness about PD and its treatment and implications thereof are critical in ensuring reduced risks for this patient population. People with PD are very dependent on their medication, and timing of this medication is critical to maintaining good symptomatic control. In the outpatient setting, the main goal of medication management for these patients is to provide as much ON time as possible while minimizing side effects of the medications, such as dyskinesia. ON time describes a period of time when the medications are working and symptoms are controlled. Patients with advanced PD may have considerable difficulty with motor fluctuations if they transition from the ON state to an OFF state when the medication effect has worn off and they are symptomatic. The fine tuning of the medication regimen is pain-staking and often the result of multiple office visits and telephone calls to arrive at the best schedule customized for the patient. This can often result in seemingly unconventional timings (sometimes on the quarter after the hour) and at time q3 or even q2 intervals. Deviations from these regimens, even as little as 15 minutes delays, can have deleterious effects on patients with PD, as detailed above.
When patients with PD enter the hospital, attention is seldom paid to the exact timing of medication administration. If a patient takes a particular medication six times daily, ordering the medication six times daily in the hospital defaults to standard timings that often are different from the patients’ own regimen, causing timing errors. Almost 75% of PD patients who enter the hospital have delays in their medications and more than 60% of these patients can have complications during their hospitalization because of these delays.
I work at the Brigham and Women’s Hospital in Boston. We call it The Brigham. A month ago we were subjected to a tragic murder of one of our doctors. The winter has been brutal and unrelenting. Then, as I was walking to work the other day I was struck by a ray of light.
It was 7:30 AM and the morning light shone directly into what was the original main operating room of the Peter Bent Brigham Hospital, one of the parent institutions of what we now know as The Brigham. Peter Bent Brigham was a restaurateur who left an endowment for a hospital for the poor. It was decided to site the Peter Bent Brigham in the Longwood area just behind the Harvard Medical School which had moved to this location in 1904.
After a national search, Harvey Cushing was selected to be the founding Surgeon-in-Chief. Cushing, a native of Cleveland and graduate of Yale College and Harvard Medical School, had trained in surgery at the The Johns Hopkins Hospital and was in the process of creating the modern field of neurosurgery. Between 1910 and 1913, Cushing worked with the architects of the new hospital and sited the operating room such that the morning sun would shine into its large window, thereby allowing the surgeons to see well with natural light.
Just over a half-century ago, in the mid-50s, at the height of our paranoia about communists and the Soviet Union, a boy sees a flying saucer land in the distance. No one else sees the event. The occupants of the mysterious spacecraft prove to be invaders from Mars. Their strategy is to capture people, one-by-one, and to perform brain surgery on them whereby an electrode controlling device is placed in the victims’ brains rendering them pawn s of the invaders, though they retain the superficial appearance of human beings. The only clue to recognizing one of these unfortunate robots is to look for the telltale antenna at the base of the hairline in the back of the neck.
In order to understand the profound meaning of the Invaders fromMars, you have to know a little neurology.
There are really two people within each of us, a fact that reflects the two almost mirror image cerebral hemispheres, each responsible for the opposite side of the body and extra-personal space. Put simply, damage to the left hemisphere will cause paralysis and loss of sensation on the right side of the body, including loss of perception from the right side of the world.
This loss of perception is more profound than simple blindness. If reflects the fact that anything that the brain does not record is actually not there. We live, after all, in virtual reality. What our brains do not sense is, for us, not there. Do the following experiment. What is behind your head? Not what you imagine might be there or what you think you remember is there. What is actually there? Is it black, white, striped? Try to describe it. You don’t have the words, because what is there is nothing, and nothing has no color, texture or shape. Is there an antenna at the base of your hairline? You couldn’t possible know, could you?
If you are reading this then you are already well aware of the current concussion crisis in the NFL. No matter where on the spectrum your opinions lie regarding this topic, there is one question that still remains: How did we get here? Surely if something has gone wrong then there must be someone to blame for it. Was it the league’s fault? The coaches? The players? The doctors? Maybe it is the injury itself that’s to blame? Perhaps it was just the perfect storm of a number of factors that put us in this situation? To truly get to the bottom of this, it is important to have a better understanding of the doctor-patient relationship. Not just in general, but specifically as it applies to concussed athletes in the NFL. Ultimately we may not find blame here, but we should at least shed some light on the realities of the situation.
As a sports medicine physician, I have taken care of thousands of concussed athletes at all levels. Eight year old hockey players, high school soccer players, collegiate football players, professional moto-cross racers and skaters, you name it. For all of them, the doctor-patient dynamic is similar. However, for the NFL players, that dynamic is entirely different. Let’s begin by looking at the usual non-NFL doctor-patient relationship.
In this month’s Archives of Internal Medicine, my colleagues and I report the results of our early experience with hospitalist co-management of neurosurgery patients. We found stratospheric satisfaction among neurosurgeons and nurses, as well as impressive cost reductions ($1400/admission). At the same time, there was no impact on quality or safety, at least as judged by hard end-points such as mortality and readmission rates.
While these results might seem like a mixed bag, I believe that the overall impact of this service has been fantastic, for patients, surgeons, and our own hospitalists. Let me explain, beginning with a brief history of hospitalist co-management, folding in the history of our neurosurgery co-management effort (which we call the “Co-Management with Neurosurgery Service”, or CNS), and ending with some of the more subtle outcomes that lead me to feel that this is one of the most important things our hospitalist program has done since its inception in 1995.
A Brief History of Co-Management
When the hospitalist field took off in the mid-1990s, we projected that its growth would largely reflect the degree to which hospitalists assumed the care of inpatient internal medicine (and later, pediatrics) patients: those with pneumonia, heart failure, sepsis, GI bleed, and the like. Sure, I recognized that there would be increased opportunities for traditional medical consultation – we come when you call us – but I completely underestimated the siren call of co-management.
It turns out that once there are hospitalists in the house, the notion of having them actively co-manage surgical patients is hard to resist, for several reasons. First, many of the problems such patients experience before and after surgery are really medical, not surgical. Secondly, just as a hospitalist can provide on-site availability that the primary care physician can’t match for medical patients, he or she can do the same for surgical patients. (In this case, it’s not that the primary care doc is stuck in the office, but rather the surgeon is stuck in the OR.) Third, in an era of more widespread quality measurement and reporting, it seems likely that a hospitalist will improve quality measures such as DVT prophylaxis and evidence-based management of CHF more than a surgeon, flying solo, would be able to.