Afferent Corp. Targets Sensory Signals as Novel Neurorehabilitation Strategy

by David Pope, editorial director

Afferent Corp. of Providence, RI, is pioneering a new class of neuromodulation devices that target afferent, or sensory, signals from the peripheral nervous system. Unlike most current neuromodulation devices that use electrical stimulation to activate the efferent neural pathways of the central nervous system, Afferent’s technology uses electrical or mechanical stimulation to increase sensory feedback from mechanoreceptors in skin, muscles, tendons, and ligaments. Building on early studies that demonstrated subthreshold sensory stimulation enhances tactile sensation and balance control in adults, Afferent initially is focusing on developing platforms for stroke rehabilitation, diabetic neuropathy, and improving balance and gait in elderly people.

Afferent’s technology is based on work by James Collins, professor of biomedical engineering at Boston University, who showed that low-level stochastic, or random, vibrations improved sense of touch. Collins went on to demonstrate that generating a subthreshold noise in the sensory pathways with a random electrical stimulation improves detectability of weak mechanical stimuli. These two experiments and others indicated that either mechanical vibrations or electrical stimulation can be used to enhance tactile sensation.

Sensory neurons adapt and cease to respond to constant or regular periodic input—for instance, we become unaware of the touch of clothing. But when exposed to random noise, sensory neurons are unable to adapt and remain in a heightened state but below firing thresholds. In physics, the use of random noise to improve the performance of a nonlinear system is called stochastic resonance, and the phenomenon has been studied in laser pumping and chemical reactions. It also has been used to explain climatic fluctuations and how crayfish sense predators in turbulent water. Collins was the first to demonstrate stochastic resonance in the human sensory nervous system.

In 1999 entrepreneur Jason Harry, who had served as vice president of research engineering at NMT Medical, Inc. which specialized in cardiovascular implants, licensed the stochastic resonance technology from Boston University and received help from the Community Technology Fund—the university’s technology transfer incubator. The following year the company Harry founded, then named Sensory Technologies, received assistance and funding from the Rhode Island state-financed Slater Center for Biomedical Technology and raised $1 million from Pharos LLC, an investment firm headed by George Hatsopoulos, founder of Thermo Electron Corp.

The initial goal was to develop shoe insoles and possibly gloves or sleeves for treating neuropathy in diabetics and improving balance in the elderly. Then in 2001, Harry decided to switch to developing products that would accelerate healing of sports injuries in the hope that this market would attract investors. The name of the company was changed to Afferent Corp. to emphasize how its technology differs from other neurostimulation technologies. The sports medicine effort failed to gain the interest of investors, and Harry had to downsize his company to himself and his first employee, James Niemi. The new focus was the development of products for rehabilitating stroke survivors and improving balance in elderly patients. Harry admitted that the firm had difficulty deciding which products to develop first because the technology could be applied to so many neurological dysfunctions.

At the beginning of 2003 the Slater Center, Boston University, and Pharos gave the company $300,000 to continue operations until a Phase II SBIR grant from the National Institute of Child Health and Human Development was finalized. The $750,000 grant for product development and clinical testing of technology to improve balance in elderly people was announced in August. Afferent had previously been awarded Phase I grants from various NIH agencies. In 2004 Afferent received another $750,000 Phase II SBIR grant from the National Institute of Neurological Disorders and Stroke to advance product development and clinical trials of the technology for stroke rehabilitation and for animal testing. By 2007 Afferent had received a total of $2.5 million in grants from the NIH.

A Series A round led by New Science Ventures raised $4 million in 2004 from Point Judith Capital Partners, Long River Ventures, Village Ventures, and Nitta Corp. of Japan, a developer of industrial robotic products including pressure and tactile sensors. All of Afferent’s previous institutional investors also participated.

Several pilot clinical studies at the Spaulding Rehabilitation Center and Beth Israel Deaconess Medical Center, both Harvard affiliated, provided evidence that imperceptible electrical stimulation improved sway balance and tactile sensations in older adults, in patients with stroke, and in patients with diabetic neuropathy. Other pilot studies showed that applying mechanical vibrations to the soles of the feet improved sway balance in the elderly and in stroke and diabetic patients. Animal studies are being conducted at Brown University and the Canadian Centre for Behavioural Neuroscience at the University of Lethbridge, Alberta. Post-stroke rehabilitation clinical studies are underway at Northwestern University’s Feinberg School of Medicine and at the Rehabilitation Institute of Chicago, and Afferent is negotiating additional post-stroke rehabilitation trials at other leading centers.

Harry, the founding CEO of Afferent, stepped down in 2006 and brought in a seasoned medical device industry executive, David Hable, as CEO and president. Hable formerly was worldwide president of Codman & Shurtleff, a neurosurgery medical device division of Johnson & Johnson. He also served as CEO and president of Brainsgate Ltd., an Israeli neurotech firm developing a novel technology based on stimulating the sphenopalatine ganglion to induce cerebral vasodilation.

Harry moved to the position of executive vice president and chief technology officer. James Niemi, who previously had worked with Harry at NMT Medical, is now VP of research, and Scott Kellogg is VP of product development. The company has eight employees, and plans to add staff as the products under development approach commercialization.

Although Afferent is initially concentrating on the stroke, diabetic, and elderly balance markets, the company sees its technology as a new class of devices for treating a variety of chronic neurological dysfunctions. In addition to the immediate benefit of improving the sensitivity of mechanoreceptors, the company is pursuing the possibility that subthreshold sensory stimulation can produce permanent changes in neural pathways and restore functions in the brain through the process of neuroplasticity. One of the critical factors in successful recovery of function after stroke or brain injury is the flow of appropriate sensory information from the peripheral limbs. Increasing the sensitivity of the sensory pathways with either electrical or mechanical stimulation could improve standard rehabilitation efforts. If current animal and human studies show positive results, Afferent plans to initiate a pivotal study to determine the benefits in stroke rehabilitation of combining sensory stimulation with physical therapy.

Mechanical and electrical stimulation devices are both under development. A device that combines mechanical and electrical stimulation is being investigated. In such a device, a mechtrode on the skin would generate surface mechanical stimulation to the skin and electrical stimulation to deeper structures. Another approach being developed by Afferent is the use of implanted electrodes to boost sensorimotor functions in patients with more severe sensory loss and motor dysfunction.

The company’s technology base attracted the attention of a major orthopedics company, Stryker Corp., which invested an undisclosed amount in Afferent in January 2007. For its investment, Stryker gains an insider’s view of the technology as it unfolds. The deal was negotiated by Stryker Development, which finds new business opportunities for its parent.

According to Hable, the Stryker investment is an important validation of Afferent’s technology. “They see the neuro area as an attractive, strategic market, both for stand-alone applications and for areas that are complementary to their existing product lines,” he said in an interview with Neurotech Business Report.

Stryker’s revenue was $5.4 billion in 2006, and about one-third came from outside the U.S. It operates two major divisions, orthopedic implants, and medical and surgical equipment. Stryker also operates almost 500 outpatient physical therapy centers in the U.S. When

Afferent is ready to market a vibrating insole or an electrical stimulation device to improve balance in the elderly, it is possible that Stryker’s physical therapy centers would be an ideal way to reach a large customer base. Similarly, when Afferent develops implanted devices, Stryker’s orthopedic group might offer to market them.
The Stryker deal also will help smooth the way for Afferent’s Series B round, which is expected to raise $15 million for product development and clinical trials that could pave the way for FDA approval of Afferent’s first product.