William A. Bauman, MD
Director VA RR&D National Center of Excellence
for the Medical Consequences of Spinal Cord Injury
Jame J. Peters VAMC, Bronx, New York
Professor of Medicine and Rehabilitation Medicine,
Mount Sinai School of Medicine, New York, NY
(718) 584-9000 ext 5428
Before the development of the Spinal Cord Damage Research Center, Dr. Bauman was a Veterans Affairs Career Development Awardee, mentored by Dr. Rosalyn S. Yalow, a Nobel Laureate in Physiology and Medicine. His undergraduate work was performed at Harvard University, and, in 1976, he received his medical degree from the State University of New York, Downstate. Dr. Bauman is board certified in Internal Medicine with a subspecialty in Endocrinology & Metabolism.
Working with Dr. Yalow, Dr. Bauman spent ten years affiliated with Solomon A. Berson Research Laboratory at the Bronx VA Medical Center. Since 1989, he has been a faculty member of the Icahn School of Medicine at Mount Sinai, at which time Dr. Bauman had the opportunity to begin to address the medical issues in a comprehensive and systematic way that were often overlooked after becoming paralyzed due to a spinal cord injury in order to improve the health and quality of life.
The Spinal Cord Damage Research Center was established with strong support from the Director of the Bronx Veterans Affairs Medical Center, the President of Mount Sinai School of Medicine, and the academic department heads in Rehabilitation Medicine, Urology, Neurology and Neuroscience. With initial generous funding from the Eastern Paralyzed Veterans of America through Mount Sinai School of Medicine, and the Department of Veterans Affairs’ Office of Research & Development, the Center had the capacity to rapidly begin addressing a variety of problems that result after a person becomes spinal cord injured.
Dr. Bauman has been a leader of several nationwide studies and has published over 300 original scientific publications, review articles, and book chapters, all of which focus on the medical consequences associated with medical complications, or related considerations, that arise in the aftermath of a spinal cord injury. He has received prestigious awards and has been asked to give state-of-the-art lectures at the annual meeting of every major national and international medical association whose mission is to improve the health and wellbeing of persons with spinal cord injury.
Collaborating with other facilities to identify, better define, and reduce the health problems of persons with spinal cord injury, Dr. Bauman has been an active investigator associated with several rehabilitation centers that have Spinal Cord Injury Model System Centers funded by the Department of Education, National Institute of Disability and Rehabilitation Research. These model SCI centers were located at the following sites: the Icahn School of Medicine at Mount Sinai, Kessler Institute for Rehabilitation, Rancho Los Amigos National Rehabilitation Hospital, and the University of Miami.
Dr. Bauman was the Chairman of the International Spinal Cord Injury Basic Endocrine and Metabolic Function Data Set and the International Extended Endocrine and Metabolic Function Data Set. He is a section editor of the Endocrinology and Metabolism section of the Journal of Spinal Cord Medicine and serves as a reviewer for several medical and rehabilitation medicine journals. He has served or chaired review panels for the Department of Veterans Affairs’ Office for Research & Development and for NIH.
Drs. Bauman and Spungen were awarded the 2014 Samuel J. Heyman Service to America Medal in Science and the Environment to recognize their impressive work to improve our understanding of the problems faced by those with spinal cord injury and treatments to improve their health and quality of life.
Program goals (Lay)
After a spinal cord injury, a person faces many challenges because of disturbances to many of the body’s function. The brain is connected to the body by the spinal cord: the brain transmits messages to the body, and the body sends messages back to the brain via the spinal cord. When the spinal cord is damaged, the body cannot properly respond to its internal environment or to the external world.
Due to limited movement and inactivity from paralysis, the body loses muscle mass and bone below the level of injury. The loss of muscle strength and reduced level of activity result in the dramatic deterioration of bone that makes a person with a spinal cord injury more susceptible to fracture, especially in the legs.
The body develops a disorder in handling sugars and fats due to the severe inactivity and marked adverse changes in body composition with the loss of muscle tissue and gain of fat mass. The deleterious changes in metabolism that occur because of a spinal cord injury result in a higher risk of cardiovascular disease.
Insulin is a hormone that pushes circulating sugar into the tissues of the body. After spinal cord injury, the action of insulin in regulating blood sugar is often severely reduced. Insulin levels tend to rise, which has an unfavorable effect on fat metabolism and predisposes to cardiovascular disease.
Insulin also plays a role in the regulation of blood flow of the small vessels in the skin. Poor circulation may lead to skin breakdown and, eventually, the development of chronic pressure ulcers, which can limit mobility and independence, and, occasionally, result in severe infections and death. Investigators are trying to learn more about how insulin regulates small vessel blood flow and reduce the body’s resistance to insulin to improve wound healing, and, perhaps, prevent skin breakdown in the first place.
Pre-clinical studies in our basic science laboratory address the biochemical and molecular mechanisms for muscle and bone loss after paralysis. Once these mechanisms are more fully understood, clinical treatment interventions can be designed and tested to reduce muscle atrophy and prevent bone deterioration after paralysis and immobilization. This work is expected to enable those with spinal cord injury to be able to benefit more fully from advances in rehabilitation medicine therapies without fear of fracture.
Program goals (Scientific)
During the chronic phase of SCI, adverse changes occur in soft tissue body composition and associated disorders of carbohydrate and lipid metabolism. Profound inactivity and adverse soft tissue body composition changes that occur in individuals after SCI result in metabolic morbidity that is extremely difficult to manage with lifestyle modification alone. Glucagon-like peptide-1 is an incretin peptide originating in the gut that potentiates insulin release after a meal in a glucose-dependent manner. Glucagon-like peptide-1 agonists, such as liraglutide, are approved by the FDA for glycemic control, but they are also approved as a primary treatment for weight loss in overweight and obese individuals. Because insulin is released in association with food consumption, hypoglycemia is less of a risk with glucagon-like peptide-1 than with some of the other anti-diabetic agents. We will determine the effect of a lone-active glucagon-like peptide administration in persons with chronic SCI who have impaired glucose tolerance and/or insulin resistance on insulin resistance, pancreatic insulin secretion, and body fat, with special interest on the visceral fat compartment.
Cutaneous microvascular blood flow is regulated by multiple mechanisms, including by insulin and by the sympathetic nervous system. In insulin-sensitive individuals, this “vasomotion” is thought to involve the activation of the vascular smooth muscle, with vasodilatation occurring through nitric oxide and vasoconstriction through the sympathetic nervous system and endothelin-1. In persons with spinal cord injury, a disproportionately high prevalence of insulin resistance and diabetes mellitus has been reported. We postulate that insulin resistance, in combination with the added consequence of sympathetic nervous system impairment below the neurological level of injury, contribute to hemodynamic dysregulation and a variety of medical complications, including pressure ulcer formation and decreased wound healing. We have demonstrated that the sub-lesional blood perfusion response to iontophoresis with insulin is blunted in euinsulinemic persons with motor-complete spinal cord injury. To gain further understanding of this finding and provide additional insight on its potential implications, an observational trial is being performed to determine the hemodynamic actions of insulin in individuals with motor-complete lower extremity muscle paralysis due to SCI and varying levels of systemic insulin sensitivity.
Because there is a dramatic loss of bone below the level of lesion after motor-complete SCI, our group of investigators has tested various pharmacological or mechanical interventions in an attempt to reduce or prevent bone loss after acute injury. In persons with motor-complete SCI, we have investigated the use of bisphosphonates (pamidronate and zolendronate) to prevent bone loss at the knee, the skeletal site that is at the greatest risk of sustaining a fracture, and we found that agents in this class of medications were not efficacious in reducing bone loss at the knee. We are presently testing the effect of an agent in a new class of drugs, a RANKL antagonist, called denosumab (Prolia) to prevent osteoporosis in persons who have motor-complete spinal cord injury. (clinicaltrials.gov NCT01983475). Our group also is interested in testing the efficacy of Prolia administration to prevent bone loss after motor-incomplete spinal cord injury, which our investigators will test in the near future. This work is anticipated to enable persons with spinal cord injury benefit more fully from emerging rehabilitation medicine therapies (e.g., neurorepair, activity-based rehabilitation, and exoskeleton technologies for ambulation) and to improve health and quality of life for the disabled Veterans.
In conjunction with Kessler Institute for Rehabilitation, investigators will be testing the effect of standing versus standing with electrical stimulation of the legs with or without testosterone replacement therapy to prevent bone loss in persons with motor-complete spinal cord injury. We are hopeful that new pharmacological agents in combination with mechanical interventions will be effective in preventing loss of bone mass and preserving architectural integrity after compete motor SCI.
Another potentially exciting area of investigation will be to use sclerostin antagonists, to prevent bone loss after acute motor complete injury. In animal studies of complete motor spinal cord injury performed in our unit, sclerostin antagonists have efficacy to almost totally prevent loss of bone mass of the hind leg at the knee. Sclerostin antagonists are presently in phase III clinical trials for postmenopausal osteoporosis in the general population, and once they receive approval for this indication, we envision testing this class of agents in our acutely and chronically injured spinal cord population.