In its May 2003 issue, PN Magazine was the first to report the development of a novel, function-restoring, olfactory-tissue-transplantation procedure. Because of my involvement in this reporting, I’ve attempted to stay abreast of developments and periodically inform readers. This update specifically summarizes the results of a recently published scientific study assessing the improvements generated from using the procedure in individuals with SCI.

Developed by Portuguese neuropathologist Dr. Carlos Lima and his colleagues, the procedure implants regeneratively endowed olfactory tissue isolated from the patient’s nose into the spinal-cord injury site. Because olfactory tissue is exposed to the air we breathe, it contains cells with considerable turnover potential, including renewable neurons, stem cells, and olfactory ensheathing cells (OECs). Briefly, stem cells are progenitor cells that have the potential to transform into a wide variety of tissue, including neuronal tissue; and OECs promote axonal regeneration by producing insulating myelin sheaths around axons.

Published in a 2009 issue of the journal Neurorehabilitation and Neural Repair, Lima’s team reported the results of transplanting olfactory tissue into 20 patients with SCI followed by extended, aggressive physical rehabilitation. The investigators believe that three treatment components are critical for functional improvement: 1) transplanting stem-cell-containing olfactory-tissue (i.e., not just isolated OECs), 2) cleaning out injury-site scar tissue to make room for transplanted tissue and to remove regeneration barriers, and 3) intense rehabilitation.

Patients were required to carry out extensive physical rehabilitation both before and after transplantation. Because there is an understandable desire to maximize the functional benefits after any cell-transplantation procedure, patients tend to rehabilitate much more aggressively after transplantation than before. By so doing, it becomes difficult to attribute any restored function to merely the transplantation. In other words, improvement may be due to a now highly motivated individual doing a lot of physical rehabilitation.

SUBJECTS

Ranging in age from 19 to 37 (average 30) years, 17 men and three women were enrolled in the study. The time lapsing from injury to transplantation varied from 1.5 to 16 years. Because all subjects had chronic injuries, relatively little additional recovery would be spontaneously expected, and, as such, any improvement is most likely due to the intervention. Injuries were sustained from traffic (14), sports (4), and work accidents (2). Thirteen subjects had cervical injuries ranging from the C4 to C8 level, and seven had thoracic injuries ranging from the T5 to T12 level.

Patients were assessed using the ASIA-impairment scale in which injuries are classified on a scale ranging from grade A, representing a sensory-and-motor complete injury, to grade E indicating complete recovery. Using this scale, 15 subjects had grade A and five grade B (motor complete) injuries at the time of transplantation. Because the injury-site scar tissue is removed as a part of the procedure, all lesions had to be less than three centimeters (~1.2 inches) in length for cervical injuries and four centimeters for thoracic injuries.

PHYSICAL REHABILITATION

Subjects averaged 32-hours per week rehabilitation for 35 weeks before transplantation, and postoperative rehabilitation averaged 33 hours per week for 92 weeks. Rehabilitation was undertaken at three centers, two in Portugal and one in Italy. One center used robotic bodyweight-supported treadmill training, and the others used an assisted over-ground-walking training with weight bearing on the hips and feet to promote sensory and muscle-movement feedback.

Results indicated that the latter approach was much more effective in promoting functional improvement after transplantation. The investigators now believe that this method allows the freedom to promote the development of new movement patterns that enhance functional connections.

RESULTS

Various functional status assessments were carried out before and periodically after transplantation. Average duration of follow-up was 28 months.

Impairment Scales: Eleven of the 20 subjects improved one grade or more using ASIA-impairment evaluations. Specifically, six improved from grade A complete injury to grade C (regaining some sensation and motor function), three from grade B (motor complete) to C, and two from grade A to B (i.e., recovery of some sensation).  Although there was considerable patient variability, on average, motor-function, light-touch, and pin-prick scores all improved.

Walking: Thirteen subjects from two of the three study centers were evaluated for ambulatory improvements using the “Walking Index for Spinal Cord Injury,” a measurement which assesses the amount of assistance required for ambulation. All 13 demonstrated some improvement using this evaluation, one progressing from no mobility to walking 10 meters with braces and crutches.

Functional Independence:  The same 13 subjects were also evaluated for their ability to carry out various activities of daily living and self care (e.g., eating, grooming, bathing, etc) by using of the FIM scale (Functional Independence Measure). The scale is a predictor of the amount of assistance or adaptive equipment an individual may need in everyday life. All subjects improved their FIM scores after the transplantation-rehabilitation intervention.

Anal:  Of the 15 subjects without anal sensation at the baseline evaluation, nine recovered some feeling. Before the intervention, no subject was able to do anal contraction, an ability recovered by five afterwards.

Bladder: Of the 15 patients without bladder sensation at baseline, five regained the ability to sense bladder fullness. One patient recovered bladder control.

Nerve Conduction: Electrophysiological nerve-conduction evaluations indicated that 15 subjects could direct signals to previously paralyzed muscles.

CONCLUSION

Lima’s team cautiously concluded that olfactory-tissue transplantation is relatively safe and possibly beneficial in people with chronic SCI when combined with postoperative rehabilitation. They also emphasized that neither rehabilitation nor transplantation alone is sufficient to promote recovery; both are needed. Furthermore, the nature of the rehabilitation is extraordinarily important in the formation of nascent, function-restoring, neuronal connections.

In a 2010 commentary, Editor-in-Chief of Neurorehabilitation and Neural Repair Dr. Bruce Dobkin (University of California, Los Angeles) notes that Lima’s study has important implications for future SCI-focused, cell-transplantation studies and asks the following questions:

1) “Does the type and intensity of the rehabilitation intervention hold one of the keys to increasing the likelihood of successful effects of cellular interventions?”

2) “Do mechanisms of activity-dependent plasticity [i.e., neuronal adaptability] provide cell signals that make the implants more functional?”

3) “Can a randomized clinical trial be considered a scientifically sound comparison, unless a design like that of Lima and colleagues is employed…?”

In recent years, I’ve looked at numerous SCI-focused, cell-transplantation programs emerging throughout the world. A number of them seem to produce astonishing results in some individuals, while the results of seemingly comparable programs are more limited. In these emerging transplantation programs, success will be in the details, one of which is apparently the right type of physical rehabilitation.

Adapted from article appearing in June 2010 Paraplegia News (For subscriptions, call 602-224-0500) or go to www.pn-magazine.com. 

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