The Mobility Foundation Center recently awarded three grants totaling $205,000. These projects support the mission of the Foundation, and we are excited to be able to contribute to this research. The awarded projects are listed below:

Motor Adaptation of Unanticipated Locomotor Transitions in Individuals with Parkinson’s Disease

PI: Nicholas Fey, Ph.D.

The goal of this proposal is to identify the motor learning processes involved in the locomotor transitions of individuals with and without Parkinson’s disease under varying levels of task anticipation and complexity. A global metric of performance will be defined as the average error of the body center-of-mass from a designated path of movement. Primary outcomes will be the rate of adaptation of this metric for repeated exposures of each condition, as well the final projected steady-state value. To understand how these aggregate outcomes are mediated, the team will assess the underlying neuromechanical responses at the joint and muscle level using a comprehensive set of kinematics, kinetics, and electromyography (EMG).

Imaging Mitochondrial Function in Brain of Patients with Mobility Disorders

PI: Jae Mo Park, Ph.D.; Co-PI: Joseph Maldjian, M.D.; Co-PI: Craig Malloy, M.D.

The fundamental purpose of this project is two-fold: 1) to acquire equipment tailored to human brain imaging using hyperpolarized 13C, and 2) to support early studies in patients with traumatic brain injury (TBI). The intent is to distinguish metabolism of physiological substrates through either normal oxidative pathways in mitochondria versus metabolism through anaerobic mechanisms to lactic acid. Although the focus is TBI, it is conceivable that hyperpolarized 13C imaging of mitochondrial function could prove valuable in a wide range of patients with movement disorders such as patients with prior strokes, inborn errors of metabolism, and multiple other conditions.

Selective Nerve Root Blocks & EMG Predicting Outcomes in Lumbosacral Radiculopathy

PI: Kavita Trivedi, D.O.; Co-PI: Thiru Annaswamy, M.D.; Co-PI: Carlos Bagley, M.D.

The objective of this research project is to evaluate the diagnostic accuracy of using selective nerve root block (SNRB) and needle electrode myography (EMG) in predicting short term outcomes pre-injection, post-injection, and postoperatively in patients with suspected lumbar radiculopathy. Hypothesis: There will be a positive correlation between the outcome of SNRB, EMG, and surgical outcomes.

Effects of selective percutaneous myofascial lengthening on gait, activity, and participation in children with spasticity

PI: Susan Simpkins, PT, Ed.D.; Co-PI: Didem Inanoglu, M.D.; Co-PI: Rami Hallac, Ph.D.

The purpose of this prospective study is to quantify the impact of selective percutaneous myofascial lengthening (SPML) on upright mobility using instrumented three-dimensional motion analysis. Study participants will be seen at Children’s Health℠ Children’s Medical Center for kinematic and kinetic analysis once before the SPML procedure and twice after the procedure to quantify the changes in gait. Clinical measures of muscle function, activity, and participation will also be administered before and after SPML to determine the effects of the procedure on the child’s daily function. Hypotheses include: an increase in amplitude of lower extremity joints during gait, an increase in power generated at lower extremity joints during gait, an increase in gait velocity on the 30-second walk test, an increase in scores on the Gross Motor Function Measure in Dimension E, which assesses walking, running, and stair climbing, and an increase in scores on the Pediatric Quality of Life Scale.

Targeting Human Amyotrophic Lateral Sclerosis

PI: Chun-Li Zhang, Ph.D.; Co-PI: Meng-Lu Liu, Ph.D.; Co-PI: Tong Zang, Ph.D.

The purpose of this study is to identify bioactive small chemical compounds that can rescue the pathophysiology of human ALS motor neurons by using a novel rat model. The pilot study that ultimately led to this proposal showed that ALS human induced motor neurons (hiMNs) exhibit poor survival resembling degenerating human motor neurons in ALS patients. This survival deficit provides a robust means for screening therapeutic compounds. For this project, the investigators will focus on chemical libraries consisting of a unique and diverse collection of small molecules with validated biological and pharmacological activities. Any validated positive hits from this unique chemical collection will be ideal candidates for further therapeutic development because of their known pharmacological activities. The investigators hypothesize that hiMNs from adult human patients constitute a unique preclinical model system and offer an unprecedented opportunity to identify therapeutics for adult-onset human ALS disease.

Publications

• Tang Y, Liu ML, Zang T, and Zhang CL. Direct reprogramming rather than iPSC-based reprogramming maintains aging hallmarks in human motor neurons. Front. Mol. Neurosci. 2017. https://doi.org/10.3389/fnmol.2017.00359. PMID: 29163034.
• Wang LL and Zhang CL. Engineering new neurons: In vivo reprogramming in the mammalian brain and spinal cord. Cell & Tissue Research 2017 Nov 23. doi: 10.1007/s00441-017-2729-2.
• Chen C, Zhong X, Smith DK, Tai W, Yang J, Zou Y, Wang LL, Sun J, Qin S, and Zhang CL. Astrocyte-specific deletion of SOX2 promotes functional recovery after traumatic brain injury. Cerebral Cortex 2017. https://doi.org/10.1093/cercor/bhx303
• Ahmed A, Wang LL, Abdelmaksoud S, Aboelgheit A, Saeed S, and Zhang CL*. Minocycline modulates microglia polarization in ischemia-reperfusion model of retinal degeneration and induces neuroprotection. Scientific Reports. 2017 Oct 25;7(1):14065. doi: 10.1038/s41598-017-14450-5.
• Wang LL, Su Z, Tai W, Zou Y, Xu XM, Zhang CL. The p53 Pathway Controls SOX2-Mediated Reprogramming in the Adult Mouse Spinal Cord. Cell Rep. 2016 Oct 11;17(3):891-903. doi: 10.1016/j.celrep.2016.09.038. PMID: 27732862.
• Smith DK, Yang J, Liu ML, and Zhang CL. Small molecules modulate chromatin accessibility to promote NEUROG2-mediated fibroblast-to-neuron reprogramming. Stem Cell Rep. 2016. http://dx.doi.org/10.1016/j.stemcr.2016.09.013

Feasibility and Functional Outcomes of a Novel Home-Based Rehabilitation Coach System for Patients with Mobility Impairment Post-Stroke

PI: Thiru Annaswamy, M.D., B. Prabhakaran, Ph.D., Una Makris, M.D.

The primary goal of this project is to design and develop a home-based rehabilitation coach system for patients with impaired mobility post-stroke. The secondary goal is to evaluate the feasibility and preliminary functional outcomes of this system in a sample of these patients. This proposed pilot study would work to expand utility of virtual reality and haptics technologies in a novel tele-rehabilitation system. We have designed and developed game-based exercise programs with voodooing that visually depicts exercises using segmented simulations. We hope that using this program will improve compliance and adherence to home-based rehabilitative exercise programs and will therefore improve effectiveness of such interventions in the long-term.