Peripheral nerve injuries represent a major public health problem, seen frequently in patients admitted to level I trauma centers and in as many as 30% of individuals with traumatic brain injuries. A primary goal of intervention in this arena is t hasten recovery so as to restore function as rapidly as possible. Progress towards this goal, however, has been limited. Interestingly, we recently discovered that systemic erythropoietin (EPO) administration speeds functional recovery after experimental crush injury to the sciatic nerve, even when EPO is administered one week after injury. These findings have already led to clinical studies being initiated overseas. Understanding how EPO induces this beneficial effect would enable us to design conditions and dosing strategies that can optimize its therapeutic effects;this is the goal of th3e studies proposed in this application. In the first Specific Aim, we will address the question of whether local delivery of EPO, rather than systemic delivery, will enable us to further enhance recovery and thus set the stage for the development of innovative local delivery methods to enhance/induce repair. The pleiotropic multi-organ effects of EPO, coupled with the surgical and medical focus for local treatment for local traumatic injury argues for a local application of this potent pharmacologic bio-modulator. This, in effect, focuses the effect of EPO directly at the site of injury, eliminating secondary effects and enabling the optimization of treatment in a clinically relevant and targeted manner. In the second Specific Aim, we will test the hypothesis that at least part of the mechanism of EPO action derives from beneficial effects on Schwann cells, the cells that support the function of peripheral nerves by myelinating the axons that run through these nerves. Overall, the identification of target cell(s) of EPO action will better enable us to determine how benefit occurs. In this Specific Aim, we will also begin teasing apart the underlying signaling that supports the impact of EPO, providing a basis for envisioning adjuvant therapies that focus on manipulating the key signaling players in the EPO receptor pathway. The above Specific Aims will represent the research training component of the proposed program to support the transition of Dr. John Elfar MD, a clinician/surgeon who is expanding his academic role to the clinician scientist track. The proposed research training plan is positioned on the backdrop of a robust mentoring and didactic training program that collectively represents a multi- faceted training environment aimed at ensuring successful career transition for Dr. Elfar.

Public Health Relevance

This application lays out a mentoring, research and didactic training program to support the transition of Dr. John Elfar MD, an Orthopaedic Surgeon at the University of Rochester Medical Center, to the clinician scientist track. In addition to specific coursework and mentoring activities, a research program is proposed that aims to test the efficacy of erythropoietin as a novel and innovative therapy for neurorecovery following nerve compression injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08AR060164-01A1
Application #
8441814
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Panagis, James S
Project Start
2013-01-01
Project End
2017-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
1
Fiscal Year
2013
Total Cost
$84,915
Indirect Cost
$6,290
Name
University of Rochester
Department
Orthopedics
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Brodell, David W; Jain, Amit; Elfar, John C et al. (2015) National trends in the management of central cord syndrome: an analysis of 16,134 patients. Spine J 15:435-42
Lee, Daniel J; Elfar, John C (2015) Dorsal distraction plating for highly comminuted distal radius fractures. J Hand Surg Am 40:355-7
Elfar, John; Menorca, Ron Martin Garcia; Reed, Jeffrey Douglas et al. (2014) Composite bone models in orthopaedic surgery research and education. J Am Acad Orthop Surg 22:111-20
Mahmoud, Mostafa; El Shafie, Sherif; Menorca, Ron M G et al. (2014) Management of neglected Bennett fracture in manual laborers by tension fixation. J Hand Surg Am 39:1728-33
Stanbury, Spencer J; English, Christopher; Yaseen, Zaneb et al. (2014) The Effect of Pulley Reconstruction on Maximum Flexion, Bowstringing, and Gliding Coefficient in the Setting of Zone II Repair of FDS and FDP: a Cadaveric Investigation. Hand (N Y) 9:99-104
Mahmoud, Mostafa; El Shafie, Sherif; Coppola, Erin E et al. (2013) Perforator-based radial forearm fascial flap for management of recurrent carpal tunnel syndrome. J Hand Surg Am 38:2151-8