Advances in bioelectronic medicine are leading to improved diagnostic and treatment options for a range of diseases. One area recently benefiting from innovation in this field is the treatment of essential tremors (ET). This neurological condition causes rhythmic shaking of a patient’s hands, head, trunk or legs, often negatively impacting their ability to carry out everyday activities. To overcome the limitations associated with traditional therapeutic approaches, Cala Health has developed a non-invasive wrist-worn device that delivers individualized bioelectronic therapy (transcutaneous afferent patterned stimulation – TAPS) for hand tremor.
Technology Networks spoke to Renee Ryan, Cala Health’s CEO, to learn more about the technology and its development. In this interview, Renee also discusses the history of bioelectronic medicine and her thoughts on where the field could be headed.
Anna MacDonald (AM): Can you give us an overview of how electricity has been used as a medicine historically?
Renee Ryan (RR): Electricity has long been used for medical treatment – starting initially with pacing of the heart in the 1950s and the emergence of deep brain stimulation (DBS) in the 1990s.
DBS has historically been used to treat Parkinson’s disease, essential tremor and other neurological conditions. It involves implanting electrodes within certain areas of the brain and having a pectoral pocket to house the actual pulse generator, just below the shoulder.
This whole field is now being called “bioelectronic medicine” and it is seeing continued advancements. Implants are now so small that they can be injected under the skin in an in-office procedure for certain indications. There are also technologies like ours, which enable non-surgical, wearable therapies to treat chronic diseases.
AM: How have recent advances in our understanding of neuroscience furthered this field?
RR: The field of neuroscience literally blows my mind. We have seen huge strides in the science involved and importantly, how the science can influence how we clinically address the conditions of the brain.
Cala’s technology addresses hand tremors in patients with essential tremor. Ever since our founding in 2014, we have gained significant insights into how a loss of input caused by age or injury, into a certain region of the brain, the thalamus, creates a bursting pattern that can result in hand tremors. These bursting patterns are also seen in other medical conditions, creating more opportunities for us to evaluate our wearable solutions in more patients.
Our approach to bioelectronic medicine is unique. We combine these breakthroughs in neuroscience with cutting edge technologies to create new medical solutions. We use a proprietary waveform called TAPS, which stands for transcutaneous (across the skin), afferent (to the brain), patterned (or timed to match the patients’ needs), stimulation. We believe that TAPS can be used across all our target indications.
AM: What led you to investigate the potential of bioelectronic medicine to treat essential tremors?
RR: I met Cala’s founder, Kate Rosenbluth, in 2014. While at Stanford’s Biodesign Fellowship Program, Kate had discovered that using electricity to stimulate nerves in the wrist presented a possible alternative to existing essential tremor treatments like pharmaceuticals, invasive implantable devices and surgery. She had a background in neuroscience and engineering and had been present in many DBS procedures where surgeons had to locate the exact location in the brain to place the electrode to treat ET. They confirmed location by sweeping over the palm of the patient’s hand and hearing the sweeping sound from the brain electrodes. So, like any great engineer, she set out to reverse it. With about 13 patients treated while at Stanford and some very good early efficacy, I encouraged her to start Cala. Johnson & Johnson co-led the Series A funding with Lux Capital.
In those early days, it was all about getting more clinical data and more intellectual property. So, one of the first things Cala did was to open an Institutional Review Board-approved clinic on-site at our offices. That gave us tremendous opportunity to perform clinical studies at our offices, but almost as important was just having user testing and consumer feedback on different prototypes. We have always put the patient at the center of everything we do.
AM: Can you tell us more about how the wristband technology works?
RR: Cala therapy is the first non-invasive, personalized treatment to reduce hand tremors for adults living with essential tremor. The device requires a prescription, and we directly ship the solution to a patient’s home. Once they receive the device, they perform a “tremor task”, which is a simple 20 second postural hold that allows the device to measure a patient’s unique tremor frequency. It automatically adjusts the TAPS waveform to match the needs of each patient, so the next step is for the patient to activate the device and start a therapy session. A session runs for 40 minutes of stimulation, and at about minute 15, the patient notices and feels their tremor improving. The benefit continues to improve for the full 40 minutes and often lasts 60-90 minutes after a session is complete.
AM: What advantages does this approach offer over traditional treatments for essential tremors?
RR: Current treatments for essential tremor include medications, which carry poor side effects, and surgical alternatives, such as DBS and ablation of regions of the brain, which are highly risky. Cala therapy offers a new approach – a wearable, non-pharmacologic, non-surgical therapy. Patients have full control over the use of the technology, and we find that they use it when they want to regain control of their activities of daily living.
I recently got to know an air force veteran and essential tremor patient who shared that, prior to using Cala therapy, he felt depressed, angry and bored because he could not do the things he used to. He felt like he was not the same person and lost the life he knew. Following treatment with Cala therapy, he’s now able to resume everyday life and all the activities he used to enjoy.
It’s incredible to know that patients with essential tremor can have their daily activities restored and return to a sense of empowerment and dignity.
AM: Aside from essential tremors, what other neurological diseases could this approach benefit from?
RR: At Cala, new therapies are under development in Parkinson’s disease and other indications in neurology, as well as targets in psychiatry, cardiology and autoimmune disorders.
AM: What regulatory considerations are involved in a technology such as this?
RR: The FDA regulates all prescribed therapeutic devices through a variety of pathways. Because Cala therapy is considered a novel technology, we were able to use the “de novo” pathway for initial clearance in 2018. Our initial submission to the FDA included data from two randomized clinical trials in over 100 patients with essential tremor. As a wearable therapeutic, the safety profile is very favorable with few risks and side-effects.
AM: Where do you see bioelectronic medicine headed?
RR: Bioelectronic medicine is quickly evolving towards a digitally enabled, patient-centric future. The consumerization of healthcare means that more patients expect to take their health into their own hands while achieving more affordable care. With these expectations, the medtech industry (and bioelectronic medicine, as a subset) will need to ensure enhanced experiences for their patient base. Cala obsesses about the consumer’s healthcare journey and our goal is to delight our patients and caregivers with unique solutions.
Renee Ryan was speaking to Anna MacDonald, Science Writer for Technology Networks.