Notable Accomplishments of Miami Project Laboratories

Contributions Leading to Changes in Clinical Care

Functional Neuromuscular Stimulation (FNS)-Assisted Walking:

• In a nationwide (20-center) trial of the computer-driven Parastep® 1 assisted-walking system, Miami Project scientists contributed data on 25 of the 35 paraplegic subjects that completed the trial. This data resulted in obtaining FDA approval for such a device.
  
  The system uses electrodes taped on the skin of the legs and back to allow persons with complete paralysis to stand and walk for limited distances.
  
  
• Extensive testing at The Miami Project defined the benefits and shortcomings of Parastep® 1. The researchers are testing different applications of the system to enhance its cardiovascular and conditioning benefits.
  
  Our scientists have continued to use the Parastep system to evaluate protocols beyond the scope of the FDA-trials. The Miami Project’s controlled experiments demonstrated that Parastep training allows many subjects to walk for distances of more than a mile, and improves leg muscle mass, cardiovascular fitness and psychological measures.

Functional Neuromuscular Stimulation (FNS)-Assisted Arm Crank:

• Development, testing and publication of design specifications for a novel FNS-arm crank apparatus used to build strength and endurance in the triceps muscles in the arms of quadriplegic subjects.
  
  This system is a modification of standard arm crank ergometry cycles and provides electrical stimulation to the triceps and other muscles, targeting weak muscle groups for conditioning exercise. Plans for the modification were published for free use by the rehabilitation community.

Rehabilitation Strategies:

• The Miami Project's research programs have provided objective evaluation of therapies consisting of passive movements, stimulated movements, biofeedback and other strategies, by comparing groups of subjects in carefully controlled studies. 
  
  Such controlled comparisons are rarely possible in clinical rehabilitation settings.
  
• Pioneering evidence has been obtained by Miami Project researchers that electrically-stimulated exercise positively influences cardiopulmonary function and strengthens the immune system in paralyzed persons.

Male Fertility Research:

• The male fertility research program has conducted critical comparisons of existing techniques for sperm retrieval, and disseminated its results to the medical community at large.
  
  Techniques that permit men with spinal cord injuries to father children have been evaluated under controlled experimental conditions.
  
  
• Miami Project researchers have identified, for the first time, which critical organ dysfunctions contribute to sperm damage in SCI men.
  
  Changes in prostate and accessory gland secretions have been found that are associated with and may cause male infertility due to spinal cord injury.
  
  
• The Miami Project’s male fertility research program has participated in procedures that have resulted in a total of 37 healthy children born so far.

Surgical Strategies:

• The Miami Project has documentation of successful surgical procedures, including delayed decompression, detethering and duraplasty.
  
  Improved surgical techniques for "detethering" the chronically injured spinal cord enhanced motor function and gait in 80% of the patients.

Innovations in Intraoperative Monitoring:

• A novel method for motor-evoked-potential monitoring of pedicle-screw placement surgery, conceived and developed at The Miami Project, is now used nation-wide.
  
  This novel method uses stimulation of nerves and recording of electrical activity in muscles (EMG), during placement of stabilizing hardware in the lumbar spinal column, to guide surgeons when healthy nerve pathways are at risk.
  
  
• Miami Project researchers established the value of threshold-level multi-pulse Transcranial Electrical Stimulation in monitoring during spine surgery.
  
  This procedure utilizes a short series of small electrical shocks delivered through electrodes placed in the scalp to stimulate brain cells. This evokes muscle activity in the arms and legs if the spinal cord is conducting messages properly. Surgeons are informed immediately when muscle responses decline:  paralysis could occur within minutes if nerves are undergoing damage or if critical blood flow in the spinal cord becomes blocked.

Preclinical Research Significant to Future Clinical Trials

Description of Human Injuries:

• Miami Project researchers reported the first clear demonstration of the human spinal rhythm generator for locomotion.
  
  Partial body weight support studies over a treadmill or on a unique over-ground track are being conducted to explore and enhance the activity of these intrinsic pattern generators.
  
  
• The Miami Project initiated and is continuing to carry on a comprehensive study of the pathology of human spinal cord tissue after injury to better understand the cellular damage caused by SCI and to guide the development of innovative treatment strategies.
  
  Pioneering observations include: clear evidence of demyelination in some human SCIs, description of "solid cord" injuries in central cord syndrome, correlation of MR images with classic anatomical analysis, description of "cell-suicide" (apoptosis) in human SCI.

Neuroprotection:

• Testing of new strategies limit the secondary damage that follows SCI and causes continuing loss of function, including: mild lowering of body temperature (hypothermia), the drug Agmatine, and promising studies with Interleukin-10.  

Interleukin-10 is a bioactive molecule that naturally limits the inflammatory response and can be neuroprotective when administered soon after injury.

Regeneration:

• Direct physiological and cell biological evidence of regeneration of adult human central nervous system tissue has been obtained in two Miami Project laboratories.
  
  (1) The demonstration that adult human central nervous system neurons can regenerate when exposed to a supportive cellular environment (retinal explants on Schwann cells in tissue culture), and
  (2) the characterization of a novel reflex movement in the arms and hands of quadriplegic research subjects, in response to sensory stimulation in the foot. This develops a year after chronic cervical SCI.
  
  
• Methods to isolate human Schwann cells from the adult human nervous system were developed at The Miami Project.
  
  These have been optimized, and it is now possible to grow large populations of these growth-promoting cells. These methods are designed to be used in "autologous" grafts of a patient’s own cells.
  
  
• Design and testing of multiple combination approaches to stimulating spinal cord regeneration based upon the strategy of bridging an area of spinal cord damage using Schwann cell constructs.
  
  Added strategies include growth factors, neuroprotection and olfactory ensheathing cells. Miami Project researchers showed that ensheathing glial cells escort regenerating axons beyond Schwann cell bridges and across long distances in spinal cord tissue, where new neural connections are now being shown to restore lost functions.
  
  
• Development of genetically-engineered cell lines that helped prove the adult CNS’s ability to incorporate and guide the development of neurons.
  
  Engineering of cell lines from fetal brain that divide rapidly in the laboratory, but stop dividing at body temperature; the cells develop into nerve cells after grafting into the brain and spinal cord. The grafted cells develop site-specific configurations, demonstrating that even the adult central nervous systems retains its ability to accurately guide growing nerves.

Pain:

• Development of engineered cell lines that secrete selected neurotransmitters and/or growth factors for use in cellular therapies to alleviate chronic pain. 
  
  Engineered nerve cell lines and adrenal gland cell grafts have both proven effective in alleviating pain following nerve and spinal injury in rodents.

Contributions to Spinal Cord Injury Research Advocacy

• The Miami Project is a key component of Florida’s pioneering allocation of ongoing support for brain and spinal cord injury research and care.
  
  Beginning in 1988, Florida pioneered the designation of revenues from traffic citations and fines to finance rehabilitative care and SCI research.
  
  
• The Miami Project has created an extensive educational outreach program that provides the lay public, other scientific centers and the media with written, electronic and in-person responses to questions related to SCI research.
  
• Miami Project scientists participate in national and international symposia and research consortia.
  
  These groups have taken up our call to unite and accelerate scientific research aimed at maximizing function and quality of life after spinal cord injury, and ultimately finding a cure for paralysis.