Patients with bilateral vestibular loss (BVL) of both central and peripheral origin experience multiple problems with balance and posture control, movement, and abnormal gait.Wicab, Inc. has developed the BrainPort balance device to transmit head position/orientation information normally provided by the vestibular system to the brain through a substitute sensory channel: electrotactile stimulation of the tongue. Head-orientation data (artificially sensed) serves as the input signal for the BrainPort balance device to control the movement of a small pattern of stimulation on the tongue that relates to head position in real-time. With training, the brain learns to appropriately interpret the information from the device and utilize it to function as it would with data from a normal-functioning natural sense. Ina total of 40 subjects trained with the BrainPort, 18 have been tested using standardized quantitative measurements of the treatment effects. A specialized set of exercises, testing, and training procedures has been developed that may serve as the course of intensive physical therapy with the BrainPort balance device. Our results demonstrate consistent positive and statistically significant balance rehabilitation effects independent of aging and etiology of balance deficit.
The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially "druggable" point of intervention. To deliver the safety profile required for chronic, nonlife threatening pain indications, highly kinase-selective Trk inhibitors with minimal brain availability are sought. Herein we describe how the use of SBDD, 2D QSAR models, and matched molecular pair data in compound design enabled the delivery of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340.
BackgroundThis study sought to examine the effect of targeted physical therapy with and without cranial nerve non-invasive neuromodulation (CN-NINM), on the walking ability of people with MS who exhibited a dysfunctional gait. We hypothesized that subjects who received electrical stimulation would have greater improvement than those who had a control device after a 14-week intervention. Gait disturbance is a common problem for people with multiple sclerosis (MS). Current management may include exercise, pharmacology, functional electrical stimulation, compensatory strategies, use of assistive devices, and implanted electrical devices. We have developed an effective rehabilitative strategy using neuromodulation of the cranial nerves via electrical stimulation of the tongue to enhance the plasticity of the brain.MethodsThe study is a within-subject blinded randomized control design. Twenty chronic MS subjects with an identified gait disturbance were assigned to either an active or control group. Both groups completed a 14-week intervention program using a standardized combination of exercise and a device that provided electrical stimulation to the tongue. Those in the active group received electrical stimulation on the tongue that they could perceive. Those in the control group used a device that did not provide a physiologically significant stimulus and was not perceivable. Subjects were assessed with the Dynamic Gait Index (DGI).ResultsThe DGI scores improved for both groups. There were significant between-group differences, with the active group showing statistically greater improvement than the control group mean.ConclusionPeople with MS demonstrated improved gait with CN-NINM training in a pilot randomized controlled trial. This study suggests that tongue-based neurostimulation may amplify the benefits of exercise for improving gait in people with chronic MS.
Vestibular dysfunction of either central or peripheral origin can significantly affect balance, posture, and gait. We conducted a pilot study to test the effectiveness of training with the BrainPort® balance device in subjects with a balance dysfunction due to peripheral or central vestibular loss. The BrainPort® balance device transmits information about the patient's head position via electrotactile stimulation of the tongue. Head position data is sensed by an accelerometer and displayed on the tongue as a pattern of stimulation. This pattern of stimulation moves forward, backward, and laterally on the tongue in direct response to head movements. Users of the device were trained to use this stimulation to adjust their position in order to maintain their balance. Twenty-eight subjects with peripheral or central vestibular loss were trained with the BrainPort balance device and tested using the following standardized quantitative measurements of the treatment effects: Computerized Dynamic Posturography (CDP) using the Sensory Organization Test (SOT), Dynamic Gait Index (DGI), Activities-specific Balance Confidence Scale (ABC), and Dizziness Handicap Inventory (DHI). All subjects had chronic balance problems and all but one had previously participated in vestibular rehabilitation therapy. The scores on the clinical tests upon entry into the study were compared to their scores following training with the BrainPort balance device. Our results exhibit consistent positive and statistically significant improvements in balance, posture and gait. These results exceed what could normally be achieved in three to five days of traditional balance training alone. Since this was not a controlled study, we are unable to distinguish the degree to which these improvements are attributable to training with the BrainPort balance device versus the balance exercises performed by all subjects as a part of the BrainPort training sessions. Nonetheless, after training with the BrainPort balance device, all subjects demonstrated significant improvements in performance beyond what might be expected from conventional vestibular rehabilitation therapy.
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