Realizing the Promise of Neuromodulation

Neuromodulation therapy (also known as neurostimulation in its simpler form) has been used to treat a number of conditions for some years now, including chronic pain and drug resistant epilepsy. This therapy, which involves delivering electrical pulses to certain nerves, has provided much needed relief to patients suffering from debilitating conditions and for whom pharmaceuticals have failed or simply don’t do enough.

Houston-based Cyberonics, a leader in epilepsy treatment, offers a product that stimulates the vagus nerve (Cyberonics merged with Sorin last year to create LivaNova); Boston Scientific and St. Jude Medical both have spinal stimulation products for pain relief; and Medtronic’s approved neuromodulation products include a sacral nerve modulation system for bladder control and a deep brain stimulation product for Parkinson’s disease. Newer players are also gaining ground in this space with recent approvals achieved by companies like Nevro, for its spinal cord stimulation for pain relief.

Today, all these neuromodulation devices have a similar form factor, derived from their predecessors: the pacemaker. The systems consist of a sizeable titanium implant can (or the implant pulse generator, also known as an IPG) containing electronics and a battery and connected to leads that deliver the electrical pulses. The devices are very expensive, ranging in cost between $20,000-$30,000, and require invasive surgery to implant the relatively large IPG and thread its leads to the appropriate location on the desired nerve. The surgery requires specialist facilities as well as expert surgeons who can carry out precise lead placement without causing harm. Given the high cost and the need for well-trained surgeons and superior facilities, today, neuromodulation therapies are offered only as a last resort after all other treatment options have failed, and thus benefit only a small portion of potential patients.

What’s more, the promise and potential of neuromodulation is not being fully realized. For example, data has shown the pharmaceutical costs for a Parkinson’s patient can be reduced from $12,000 per year to $6000 per year with the addition of neuromodulation therapy. In 2015, another study conducted by the Vancouver Island Health Authority on their Pain Program reported a 29% reduction in non-pharmaceutical costs and 31% reduction in pharmaceutical costs over three years for chronic pain patients who received spinal cord stimulation implants. However, these savings will not have a significant impact on the healthcare system unless the therapy is offered to a majority of patients, which in turn is not feasible unless the overall cost of offering neuromodulation therapy is reduced.

Even more important are the raft of new applications for neuromodulation that are being discovered by clinicians and neuroscientists as they further their understanding of neural pathways. Soon, we could have treatments for cardiovascular disorders, gastrointestinal issues, as well as conditions like depression, obesity, and other chronic diseases based on appropriate stimulation or blocking of various nerves.  Neuromodulation therapy has the potential to significantly reduce the costs of treating these types of conditions and more importantly, improve quality of life for people suffering from them. However, the medical device industry must cross a chasm in order to realize this potential.

The success of neuromodulation approaches for chronic, benign non-central nervous system (non-CNS) therapy areas, such as autoimmune diseases, is dependent upon modulation of specific, defined regions of the peripheral nerve bundles. This is similar to pharmacological therapy, in which the approach needs to optimise therapeutic efficacy by targeting the right receptor(s) involved in the disease pathway and minimizing side effects by avoiding activation of unwanted receptors. So the first key challenge to overcome is for the scientific community to accurately map the peripheral nervous system and understand the mechanism of action. This is a very active research field and we are seeing promising results.

The next step that needs attention is the preclinical in vitro and in vivo disease models. In order to validate the novel neuromodulation approaches, especially in non-CNS therapy, and rapidly enable them to be brought from research to the clinic, it is critical to develop accurate disease models that can be used to test and demonstrate efficacy of the therapies.

The “kit” or the system for delivering neuromodulation therapy must also undergo a radical change in order to be suitable for tackling specific nerve bundles in the peripheral nervous system as well as to be viable for the vast populations suffering from chronic diseases. Devices need to become smaller and move away from today’s IPG + lead configuration. Moreover, the need for expensive and specialist invasive surgery must be eliminated, to improve affordability as well as accessibility. The technology must be such that the implants can be reliably inserted by surgeons in facilities around the world, and not just in the best academic hospitals in the West. Additionally, to enable the therapy to stimulate the right nerve bundles, miniature cuff technology will be required as well as the means to prevent migration following implantation.

Today’s implant is large because it contains a relatively large battery, meant to last 7-10 years. If the implant can be powered wirelessly from outside the body, or if a smaller internal battery can be wirelessly recharged by the user, the size of the internal battery—and hence the size of implant itself—can be drastically reduced. While wireless power transfer into the body is challenging, especially when the implant might be several centimeters deep inside the body, significant research around enabling external power sources for implants is underway.

The ability to integrate the various functionalities on a “system-on-chip” is also making it feasible to miniaturize the supporting electronics required for implants. Custom Application Specific Integrated Circuits (ASICs), for instance, can deliver the functionality of an entire system on a single piece of silicon. But chip design is an expensive undertaking and only justified if the volumes are large enough. If neuromodulation therapy truly reaches the mass populations, bespoke silicon will definitely be viable at an affordable price point. Already, technology is mature enough and sufficient research is underway, which lets us believe that tomorrow’s neuromodulation implants will look very different from the large IPG-based devices of today.

A small implant will introduce new challenges for its placement, especially if minimally-invasive procedures are to be employed. There will be a need for precise surgical instruments and delivery devices that do not rely on the surgeon’s skill and do not require years of training. Moreover, with some applications targeting nerves that are deep inside the body and surrounded by blood vessels, a different generation of tools is likely to be required—one that combines sensing with implant delivery mechanisms to help with the detection of nerves or the avoidance of critical vasculature. Visualization techniques can be applied, where data received from sensors at the tip of the tool is displayed to provide the surgeon with a live picture of the anatomy without having to conduct open surgery. Such tools have the potential to greatly simplify the procedure, minimize the risk, and lower recovery time, thereby enabling a larger number of patients to access the therapy.

Another aspect that will need attention for the new generation of neuromodulation treatments is the level of user control. The “place and forget” systems of today’s implants will no longer work if stimulation is to be turned on or off, or if it requires tuning in response to the patient’s condition. Instead, we will require a simple, user-friendly means of controlling the implant from the outside. This will need to be achieved via bi-direction wireless communication with an external device, which can enable transfer of data and commands to and from the implant. This will then open up the possibility of closed-loop therapy based on measurement and understanding of the impact observed. Moreover, if re-calibration of the electrode-nerve interface via the cuff is required, it could be achieved via the remote system.

Needless to say, due attention must be paid to the security of this communication to prevent unintended interactions and ensure reliability of the actions. For example, appropriate encryption techniques and handshakes should be applied to ensure authenticity of the external device, as well as confirming the identity of the user. Different levels of control will need to be granted to different types of users, e.g. the patient and the clinician. But these are not insurmountable challenges—in fact, they have already been tackled in other areas of healthcare as well as in other connected systems we already use for everyday tasks, like banking.

Neuromodulation as a technique offers huge promise—not just for the therapies it has already been approved for, like pain relief and epilepsy, but also for therapies that are still in the research phase, including chronic conditions like depression, which affect a large number of people. Significant cost savings and quality of life benefits can be gained if these therapies are made easily available and accessible by a larger patient population.

But for this promise to be realized, and for the healthcare economics to stack up, the big boys of the implant industry need to rise to the challenge. They must be willing to take a risk and think outside the “can.” Equally important is the role of regulators and clinicians who must be willing to support the change that this will bring. The technology building blocks are available, as well as the know-how and engineering skills to push boundaries and realize the necessary solutions—I should know, I see them in our building!

While we are unlikely to see transformation happen overnight, we are hopefully not too many years away from it—and I am sure that the wait will be worthwhile. Given the recent activity and significant investment in the neuromodulation space from “outsiders” such as pharmaceutical giant GlaxoSmithKline, it is fair to say that competition will be fierce and as always, the advantage will be with those who are first to the finish line.