Current Research

Dr. Calancie’s current research focuses on two active projects: developing a translational repair strategy for cauda equina injury, and advancing SuperConditioning TMS as a biomarker of upper motor neuron function in ALS.

Both projects reflect a long-standing goal of his laboratory: to use neurophysiology not only to understand nervous system injury and disease, but to create tools that can improve diagnosis, guide treatment, and support recovery.

Cauda Equina Repair

Cauda equina injury affects the bundle of spinal nerve roots that innervate the legs, bladder, bowel, and pelvic floor. Although these injuries are often grouped with spinal cord injury, the damaged structures are not the spinal cord itself, but nerve roots that have already exited the cord.

This distinction matters. In some respects, cauda equina nerve roots may behave more like peripheral nerves than central spinal cord pathways, which raises the possibility that repair could be more feasible than repair of the spinal cord itself.

Despite this, direct repair of injured cauda equina nerve roots is rarely attempted in clinical practice. Patients may undergo surgical stabilization of the spine, but injured dorsal and ventral nerve roots are typically not repaired.

Dr. Calancie’s work in this area began at The Miami Project to Cure Paralysis, where he participated in primate studies of cauda equina repair using guidance channels seeded with autologous Schwann cells. After moving to Upstate Medical University, his laboratory continued this work in a rat model, developing methods to identify spinal nerve function and demonstrating axonal regeneration across Schwann cell-seeded repair material after immediate repair of spinal nerve transection.

Building on this foundation, Dr. Calancie and collaborators are now developing a clinically relevant pig model of cauda equina injury and repair. The goal is to test a multifaceted repair strategy in a large-animal model that more closely approximates human anatomy and surgical conditions.

A consistent principle of the project is clinical translation. Wherever possible, the approach uses products or devices already approved for other indications, and when cellular transplantation is involved, uses autologous cells derived from the subject. These choices are intended to reduce barriers between successful large-animal studies and eventual human application.

The long-term goal is to develop a functional repair strategy for cauda equina injury that can be advanced toward clinical trials.

ALS Biomarkers and SuperConditioning TMS

A second active project focuses on the development of SuperConditioning Transcranial Magnetic Stimulation, or TMSsc, as a biomarker of upper motor neuron function in ALS.

ALS affects both lower motor neurons, which directly innervate muscles, and upper motor neurons, which originate in the brain and help control voluntary movement through corticospinal and related pathways. Reliable measurement of upper motor neuron function remains a major challenge in ALS diagnosis and clinical research.

SuperConditioning TMS is a non-invasive four-pulse stimulation method developed by Dr. Calancie to study cortical connectivity and motor pathway function. The approach uses weak conditioning pulses followed by a stronger test pulse to probe inhibitory and excitatory intracortical circuits.

This method grew out of decades of work using electrophysiologic techniques to study spinal cord injury, motor cortex function, and intraoperative monitoring. In ALS, the goal is to determine whether TMSsc can provide a more sensitive and reliable measure of upper motor neuron integrity than currently available approaches.

This work has two major aims:

1. Earlier diagnosis
   ALS diagnosis is often delayed for many months after symptoms first appear. A reliable neurophysiologic biomarker of upper motor neuron dysfunction could help shorten that delay.

2. Better measurement of disease progression
   Current clinical measures may not capture subtle changes in upper motor neuron function. A more sensitive biomarker could help investigators determine whether experimental therapies are affecting disease progression.

Dr. Calancie’s recent work has also challenged prevailing assumptions about cortical inhibition in ALS, suggesting that some inhibitory motor cortex mechanisms may remain functional during voluntary contraction. These findings have implications for how TMS-based biomarkers are interpreted in ALS research and clinical trials.