An electronic system that stimulates the nerve of the diaphragm muscles received approval from the US Food and Drug Administration (FDA) for use in patients with Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s Disease or motor neuron disease. The system, called NeuRx Diaphragm Pacing System (DPS)® is said to help ALS patients breathe longer without relying on the aid of a ventilator.
The NeuRx device was approved by the FDA in September of 2011 under a Humanitarian Device Exemption, a designation given to medical devices that demonstrate safety and probable benefit for rare diseases. The device received the designation following a multi-center clinical trial that enrolled 106 patients and treated 86 for chronic hypoventilation.
Approximately 30,000 people in the US live with ALS, a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. As the phrenic nerve to the diaphragm muscle fails, most ALS patients develop reduced lung function or too-shallow breathing that requires them to have a tracheostomy or mechanical ventilator support. Of the 5,600 patients diagnosed each year, nearly 60 percent have respiratory problems. There is currently no cure for ALS.
Raymond Onders, MD, FACS, who is Director of Adult Minimally Invasive Surgery at University Hospitals (UH) Case Medical Center, Cleveland, OH, and holds the Margaret and Walter Remen Chair in Surgical Innovation, and Professor of Surgery at Case Western Reserve University School of Medicine, helped develop and test diaphragm pacing. In 1996, Onders, co-founder of Synapse Biomedical, began clinical research aimed at helping patients with spinal cord injuries breathe better, including treating the late actor Christopher Reeve in 2003. In 2004, his research expanded to include patients with ALS, whose progressive muscle weakness leads to an inability to breathe without ventilator support.
In late 2008, Onders presented the results from two clinical trials of people with ALS who received NeuRx systems, which showed that trial participants tolerated the device well and that those with declining respiratory capacity during the lead-in period to the study showed a slower rate of decline after they had pacing systems implanted. Onders lost his own sister to ALS in 2011. His development of the procedure, “diaphragm pacing via laparoscopy,” has helped to improve the lives of patients who can be freed from being tethered to a mechanical ventilator that impairs their sense of taste and smell, and reduces their ability to speak.
“I lost my sister to this devastating disease during the FDA approval process,” said Onders. “I also have seen the significant benefit diaphragm pacing can provide to patients. Diaphragm pacing has improved the breathing and quality of life of many of the patients I have treated. I am committed to searching for the cure for this disease but, until then, and with this approval, we are now able to continue helping ALS patients until that cure is found,” said Onders.
In 2008, Synapse Biomedical received approval from the FDA for the NeuRx DPS for ventilator-dependent spinal cord injury patients who lack voluntary control of their diaphragms.
The NeuRx DPS was developed over the course of 20 years through a joint effort of physicians and engineers at several institutions, including UH Case Medical Center, Case Western Reserve University, and the Veterans Administration Medical Center. Funding assistance was provided by the FDA, U.S. Surgical Corporation (a division of Covidian), University Hospitals Case Medical Center, the VA, and the National Center for Research Resources of the National Institutes of Health.
How It Works
The device, which is implanted using minimally invasive laparoscopic techniques, provides electric stimulation to the muscle and nerves in the diaphragm. When stimulated, the diaphragm contracts, conditioning the muscle and improving resistance to fatigue under normal exertion.
Surgeons make four small incisions in the abdomen and insert a laparoscope to view the diaphragm and emplace small electrodes. The electrodes are connected by wires under the skin to a small, battery-powered external pulse generator (EPG) that stimulates the movement of the diaphragm muscle, creating a vacuum-like effect in the chest cavity that draws air into the lungs. When this contraction eases, the air is expelled from the lungs. On average, this process is repeated 10 to 14 times per minute.
When the patient awakens after surgery, the device, which has no moving parts, noiseless operation, and small size, is programmed to allow an effective yet comfortable breath. Patients start with three 30-minute sessions daily. As the disease progresses, the conditioning time is increased. The device activates the diaphragm muscle, not only supplementing the patient’s breathing ability, but also delaying diaphragm atrophy and the need for invasive ventilation. (See Figure 2)
In order to benefit from the pacing system, people with ALS must have adequate function not only in the diaphragm, but in the phrenic nerves, which stimulate this muscle. The DPS can be used in conjunction with non-invasive ventilation (NIV), such as BiPAP®, received via oral or nasal delivery.
The electrodes are designed using 316 Stainless Steel and other biocompatible materials with a long history of implantation. The design of the PermaLoc® electrode has been developed with anchoring technology specifically for long-term implantation into the diaphragm muscle and laparoscopic delivery. The patient controls the generator, turning it on and off by pressing the two buttons on the front of the EPG.
Where It Stands
The NeuRx DPS was evaluated in a clinical study at nine clinical centers (eight in the US and one in France). In the study, 86 patients with ALS had breathing problems. The patients who used the NeuRx DPS plus NIV survived on average 16 months longer than patients who just used NIV. This 16-month time frame is from the time of diagnosis. Survival time was measured until death or the need for a full time ventilator and a tracheostomy. The patients who just used NIV were similar patients in a different study.
In August 2012, the Muscular Dystrophy Association (MDA) and the ALS Association announced a joint commitment to provide funding for a Phase 2 clinical trial that is expected to determine whether the DPS can cause significant improvement in respiratory function and improve quality of life for people with ALS. MDA awarded a grant totaling $750,000 over three years to support a new trial. The award was made through MDA Venture Philanthropy, the drug development arm of MDA’s translational research program. The ALS Association committed $450,000 over three years through its Translational Research Advancing Therapies for ALS program. Synapse Biomedical also is providing support for the trial.
The Phase 2 trial is expected to enroll 180 people with ALS. Of those, 120 will receive the DPS, and 60 will receive treatment in line with the current standard of care. Trial investigators will compare survival between the standard-of-care (as control) and DPS groups. In addition, the investigative team will compare measures of diaphragm function, shortness of breath, and quality of life over time between the two groups.
To view a video of how the technology works, visit http://www.techbriefs.com/tv/NeuRx-DPS.
This article was compiled with information supplied by Synapse Biomedical, Inc., Oberlin, OH. The ALS Association, and the Muscular Dystrophy Association. For more information on the device, visit http://info.hotims.com/45600-165.