The starting point: the metabolic syndrome

All the body's organs are not working independently of each other, and all undertake a small and specific portion of the overall work. Our brain coordinates them, specifically by an automatic process totally independent from our will and consciousness. This is called the autonomic nervous system (ANS).

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Examples of how the ANS works are:

  • When we are running, our body’s muscles need more blood, oxygen and glucose to work. The heart starts pumping forward more blood flow, by increasing its frequency and output. What orders the heart to do this? It is our brain, by the ANS.

  • When we start eating and our digestive system needs more blood to work, our brain orders a transfer of the needed blood from the body muscles, produces mucous and acid from the stomach, and create digestive enzymes, etc. in order to speed up intestinal movements. The ANS coordinates all the organs to start digestion, without involving our will and consciousness.

In the first above example the ANS works with the so-called sympathetic arm, and for the second example it works by the parasympathetic one, with a functional balance.

Scientific literature shows that the living beings are born with and inherit1-2 a given balance between sympathetic and parasympathetic autonomic nervous activity. The sympathetic tone increases during “emergency” situations, e.g. riding a bike up a steep hill. On the other hand, the parasympathetic tone increases during digestion and moments of relaxation.

Scientific literature shows also that when, during the resting phase, people with a high sympathetic/parasympathetic balance have shorter lives and develop many diseases, such as hypertension, cardiac failure, diabetes, all which are grouped under what is better known as “metabolic syndrome”.

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Dr. Cigaina’s hypothesis

Dr. Cigaina commenced his 20-year investigation and clinical experience with the gastric pacemaker in obese people based on a simple question: Is it possible to increase the parasympathetic tone in people born with a pathologically high sympathetic/parasympathetic (SP) ratio?

The solution proved to be the electrical stimulation of the stomach by a dedicated pacemaker, ameliorating hypertension in very obese patients, and normalized glycemia in those with diabetes type-2. These results occurred before the weight loss became evident. At the same time these improvements were always associated with a reduction of the SP ratio. The SP ratio is easily measured by the study of the cardiac variability by an ECG.

Furthermore, when the gastric pacemaker was turned on, specific brain areas were observed to react.

Dr. Cigaina has discovered the precise gastric area where the gastric pacemaker has to be applied to increase the parasympathetic tone: just a 2 cm2 in the lesser curvature.

To summarize Dr. Cigaina’ hypothesis:

The nature of a signal starting from the lesser curve of the stomach and reaching the brain nuclei of the basal ganglia is of a digestive kind. It has been observed that when the brain receives that information, the parasympathetic tone starts immediately increasing, as if a digestive process was in place.

The first solution

The initial solution Dr. Cigaina adopted to tune the SP ratio was the gastric pacemaker. With this device he collected a significant amount of data from performing about 250 implants in animals and 900 implants in humans.

The gastric pacemaker been approved by the FDA to treat obesity, one of the effects of the metabolic syndrome. However it still presents several drawbacks:

  • It has to be implanted by a laparoscopy, so with an inconvenient abdominal procedure, under general anesthesia and hospital admission.

  • An elctrocatheter, or lead, is needed to connect the pacemaker to that “brain-gate” gastric area. The lead can undergo fractures over time.

  • Batteries have to be replaced requiring surgery under local anesthesia.

  • The pacemaker has to be tuned and personalized to the patient, over a long time.

Despite its problems, the gastric pacemaker proved to be very effective in treating all the diseases associated with the metabolic syndrome and it is also well accepted that the metabolic syndrome itself is closely related to an imbalance between the sympathetic tone and the (too-low) parasympathetic tone. It follows directly that if the ANS could be brought back into balance, various diseases would be treated. In addition, it has been established that the status of the ANS and the sympathetic and parasympathetic tones can be precisely measured through heart rate variability (HRV).

The step forward: the Brain NeuroModulator (BNM)

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The BNM, a brain neuromodulator called Phoenix, is a small device implantable in the lesser curvature of the stomach, through a digestive upper endoscopic procedure, inducing depolarization of that 2 cm2 sensitive area of stomach, the same position where the gastric pacemaker lead did its job.

It is specifically designed and built to obtain the same end results of its predecessor but it gets rid of all the defects:

  • No laparoscopy.

  • No leads.

  • No battery, and no current needed to get depolarization for the brain-gut area.

  • No device tuning during follow-up.

Dr. Cigaina and his team initially studied animals to find the best, most effective and safe procedure to implant a device endoscopically through an upper digestive procedure. The BNM resets an imbalance in the Autonomic Nervous System with the aim to treat functional diseases such as type-2 diabetes, hypertension, and gastroesophageal reflux disease (GERD).

The MedAutonomic team is the first to insert in a human a device in the gastric wall in a minimally invasive way.

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The device has demonstrated to be tolerated over the long term. It is sending a signal to the brain, which is confirmed by heart rate variability (HRV) as expected.

“The technology that we have developed to generate power without a battery to send a signal to the brain is important” said Paolo Fabris, chief executive officer of MedAutonomic. “We are able to harvest energy from the body, so the device can remain in the stomach wall without the need of a battery. Now that we have successfully implanted the Phoenix into the stomach of a human, we have taken a further step in developing a promising therapy for the metabolic syndrome. Our next efforts are to start, as soon as possible, the CE mark trials.”

MedAutonomic’s BNM technology has four main components.

  • A piezoelectric energy system harvests energy from the body, eliminating the need for a battery.

  • The design of a CPU that produces a precise signal in order to address the imbalance in the ANS.

  • A mechanism to send the signal to the brain through the stomach-brain axis.

  • An implantation tool (patent pending) has been developed to allow the first of its type procedure to insert a device in the stomach wall without any type of surgery.

Thanks to the technology developed by MedAutonomic, operating the endoscope and implanting the BNM requires only an endoscopist and an assistant. The outpatient procedure involves implanting the BNM in less than ten minutes. MedAutonomic is the first to insert a diagnostic and/or therapeutic device in the gastric wall in a minimally invasive manner.

The BNM directly proved to adjust the parasympathetic/sympathetic tone and rebalances the ANS. This has significant advantages over the two major competitors.

  1. Medical therapy with drugs does not repair the genetic effect, leaving the ANS unbalanced. In addition, drug resistance and side effects are often related to a long-term drug therapy. (no medical therapy for obesity is sustainable forever).

  2. The surgical therapy of functional disorders like esophageal reflux or the weak satiety in obesity does not repair the underlying genetic defect, but provides different kinds of unnatural changes of the digestive system, with several and unavoidable side effects.

Next Steps

The technical evolution and progress of Phoenix continues and are the main challenges of MedAutonomic. We plan to start CE mark trials in 2019.