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MIAMI PROJECT RESEARCH ACHIEVEMENTS

 

The broad scope of research carried out at The Miami Project has focused on answering questions that help define human spinal cord injury and reveal strategies for the repair of damaged spinal tissue.  The team has also made advances in knowledge that have improved the current care of people with SCI.  Over the last two decades, The Miami Project has made claim to several scientific achievements.

 

Pioneered the concept of a multidisciplinary approach to SCI research; assembled the most comprehensive team of researchers to address the multifaceted problems of spinal cord injury.

 

First to build a state-of-the art SCI research facility that under one roof houses the tools and technology that in the hands of researchers will provide advances to find a cure.

 

HUMAN DISCOVERIES


Established the largest collection of postmortem human spinal cord tissue in the Western Hemisphere. Pioneering anatomical observations and physiological recordings have revolutionized the understanding of human injury.

First to show conclusive evidence of chronic demyelination after SCI in humans.

First to conceive and develop a novel intraoperative monitoring technique that makes spine surgery safer. The technique is now used nation-wide and reduces the risk of paralysis during pedicle screw placement surgery.

First to provide evidence that humans possess specialized nerve circuitry that influences walking and could possibly be enhanced by rehabilitation training. These observations contributed to the development of body weight support gait training. Miami Project investigators are currently adding to the body of knowledge regarding the effectiveness of this rehabilitative training.

First to show that grip strength and sensory/motor function can be improved in people with chronic SCI by using a task practice based therapy that influences the neural circuitry for controlling arms and hands.

Completed extensive testing of a computer-driven Parastep® 1 assisted-walking system. Showed its ability to enhance cardiovascular and conditioning effects and provided supporting evidence for approval by Medicare to reimburse for the device.

First to offer proof that poor sperm motility in men with SCI is a result of chronic inflammation. New knowledge and assistive reproductive procedures have afforded the opportunity for men with SCI to father biological children. Recent Miami Project findings reveal the possibility of a rational treatment for the infertility.

Discovered that semen retrieval by penile vibratory stimulation should be the treatment of first choice for anejaculatory men with SCI because semen quality is better than when obtained by electroejaculation.

Developed new strategies for the multidisciplinary evaluation of SCI pain. The comprehensive state-of-the-art approach targets pathological, physiological, psychological and social aspects of pain in order to tailor individual treatment strategies. This combination of methods will be useful in evaluating the outcomes of spinal cord injury clinical trials.

Partnered in the first multi-center trial establishing safety and effectiveness of electronically-stimulated cycling in persons with SCI.

Provided first evidence that cardiac structural decay was reversible after electrically-stimulated cycling in persons with SCI.

Undertook first studies establishing benefits of circuit resistance exercise training on attributes of fitness and lipid disorders in persons with both paraplegia and tetraplegia.

Provided first evidence of immune system suppression as an infection risk accompanying tetraplegia.

Led only randomized multi-center trial and published the first manuscript providing evidence for beneficial effects of drug therapy on cardiovascular disease risks in persons with tetraplegia.

Provided first evidence of exaggerated post-prandial lipemia as a silent cardiac risk in persons with SCI.

Provided first evidence for linkage of post-prandial lipemia and pro-atherogenic inflammatory vascular activity.

Currently leading the first large-scale multi-center trial examining lifestyle intervention on diabetes prevention after SCI.

Generated preliminary results that indicate that perceived life interference is related to both neuropathic pain symptom severity and objective signs such as brain metabolites, using Magnetic Resonance Spectroscopy. Specifically, the metabolites associated with neuronal dysfunction or increased numbers of glial cells appear to be important.

First to attempt to directly activate the brain to improve hand function in individuals with cervical SCI. Using transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) hope to improve the ability of the brain to drive information through the remaining spinal pathways and thereby improve hand function.

First to show that muscle weakness is greater with long-term baclofen use and paralysis than with paralysis alone. This weakness makes the whole muscle more fatigable. Restoring the strength and speed of paralyzed muscles to pre-injury levels may require more extensive therapy when baclofen is used chronically. The short-term benefits of baclofen on spasticity (e.g. management of muscle spasms that may otherwise hinder movement or social interactions) therefore have to be considered in relation to its possible long-terms effects on muscle rehabilitation.

Demonstrated that the fatigability of the muscle fibers themselves increases after SCI, largely due to lack of muscle use. Transmission of the signals across the neuromuscular junction remains effective, however.

 

BASIC DISCOVERIES


Designed novel experimental strategies including mild lowering of body temperature (hypothermia) to limit secondary damage following SCI. Promising effects with Interleukin-10, and the inactivation of NFkappaB are also under investigation.

Discovered that the adult nervous system has a remarkable capacity to accept and integrate transplants of neuronal cell lines. Demonstrated that embryonic neurons can reconnect to muscle and restore its function in animals.

Initiated studies to explore whether neural precursor cells or stem cells can be developed and stimulated to mature into different types of nervous system cells.

First to establish optimal laboratory methods to isolate and expand human Schwann cells in culture from adult peripheral nerves – which represent critical steps for the use of autologous Schwann cells grafts for neural repair.

First to demonstrate remarkable improvement in walking function in animals using an innovative treatment that combined Schwann cell grafts with the administration of a cell messenger molecule (cyclic AMP) and the drug rolipram.

Created bioengineered cell line transplants that show promise in the treatment of chronic SCI pain.

Identified a signaling pathway that is activated during traumatic brain injury (TBI) within astrocytes and increases inflammatory gene expression in astrocytes, which exacerbates injury.

Used a novel aquaporin inhibitor to regulate tissue swelling after injury.

Established that systemic administration of just one dose of the immune-modulating drug rapamycin, a dose already well-tolerated in human cancer patients and given at a feasible therapeutic time window after brain injury, reduced the severity of seizures observed at 12 weeks after experimental TBI in rats.

First to demonstrate that there are TBI-induced deficits in the activation of molecules known to be critical for hippocampal learning.

First demonstration in animals that deep brain stimulation of serotonin-containing neurons promotes recovery from SCI or TBI.

Proposed and confirmed new theory that specific brainstem nuclei both detect traumatic brain and spinal cord injury and control their endogenous repair.

Discovered novel compound to promote regeneration in vivo.

Identified new family of genes that regulate the intrinsic ability of axons to regenerate.

First large screen of kinases in regeneration in mammalian neurons.

First to discover a role for cancer genes in regeneration.

Identified new descending pathways, originating in the brainstem, that regulate the spinal neurons controlling walking. This analysis has resulted in the identification of a new therapeutic target for the control of walking and research toward development of pharmacological interventions.

First to show that an endothelial bridge across the injury site forms within 7 days of contusion, this could be a bridge for early axonal growth, but disappears for a week or two before reappearing.

Demonstrated
that the addition of olfactory ensheathing cells injected into the stumps beside a Schwann cell bridge leads to long distance axonal regeneration after complete transection.

Provided
striking evidence that methylprednisolone improves axonal regeneration into Schwann cell bridges in transected adult rat thoracic spinal cord.

Established that the combination of neurotrophins BDNF and NT3 promotes supraspinal axonal regeneration into Schwann cell bridges following complete transection in adult rat thoracic spinal cord.

Revealed that NT3 delivered into a muscle is transported to the motor neurons which secreted it. This correlated with increased sprouting of corticospinal tract axons and improvements in walking across a horizontal ladder.

Discovered that by changing the application of a cell delivery matrix, the host/Schwann cell bridge interface is changed and becomes highly irregular with many astrocyte processes extending into the bridge. This is associated with a significant increase in the number of brainstem axons regenerating into the Schwann cell bridge.
 

 
 
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