Skeletal muscle plasticity in health and disease and therapeutic strategies
Supported by the UF Myology Institute, a group of internationally recognized NMPT muscle physiologists (Drs. Walter, Judge, Esser, Smuder, Forbes and Hepple) and clinician-scientists (Drs. Vandenborne, Byrne, Lott) examine the pathophysiology of skeletal muscle dysfunction associated with conditions such as disuse, aging, cancer, and neuromuscular disease. Therapeutic strategies to ameliorate loss of muscle function or to enhance recovery include pharmaceutical and/or nutritional treatments, progressive resistance training, locomotor training, gene transfer and stem cell therapies. Several investigators (Walter, Vandenborne, Lott, Judge, Bishop and Byrne) also examine the muscle damage in cachexic, senescent and dystrophic muscles. Students are exposed to studies ranging from cell cultures, to perfused muscles, in vivo animal studies and large multicenter clinical trials.
Neurodegenerative diseases and movement disorders
Many of our faculty are working to translate basic discoveries in neurodegenerative diseases such as ALS and Alzheimer’s into more effective medical therapies. NMPT mentors Drs. Bizon, Schmidt, and Okun are all active members of The Center for Translational Research in Neurodegenerative Diseases (CTRND). NMPT faculty Drs. Okun, Hegland, Vaillancourt, and Plowman are also part of the Fixel Institute. Directed by Dr. Okun, the Fixel focuses on treatment of ALS, Parkinson’s and other movement disorders. The Fixel has particular expertise in the surgical treatment of movement disorders using deep brain stimulation, but also offers clinical trials using pharmacological strategies. The NMPT program also has a group of researchers (Drs. Byrne, Fuller and Smith) examining neurodegeneration in glycogen storage disease (Pompe); this team completed the first FDA approved gene therapy clinical trial in Pompe patients.
Neural control of movement in humans in health and disease
Many of the NMPT faculty study the neural control of human movement in health and disease including Drs. Fox, Ferris, Vaillancourt, Clark, Rose, Hegland and Mitchell. For example, Dr. Ferris and his group are pioneering the use of high-density electroencephalography (EEG) to enable mobile brain imaging during walking and running in humans. This work is providing essential data regarding brain activation during control of movement. Dr. Vaillancourt and this team are using imaging and electrophysiology methods to map brain connectivity and function in health and disease, specifically Parkinson’s and Parkinsonism. In addition, NMPT faculty are actively studying the neural control of swallowing in healthy persons and those with neuromuscular disease (Hegland). This is an understudied, but very clinically important motor function – dysphagia is a motor impairment leading to morbidity and mortality in a range of neuromuscular diseases including ALS and Parkinson’s.
Imaging and neuromuscular plasticity
State-of-the-art imaging techniques play a prominent role in the research of several NMPT faculty. Drs. Vandenborne, Walter, Forbes and Lott use magnetic resonance imaging (MRI) in animal models as well as patients with muscular dystrophies to evaluate disease progression and efficacy of therapeutic approaches. An ongoing clinical trial led by Dr. Vandenborne has recently provided the first evidence for therapeutic efficacy in treating Duchene Muscular Dystrophy using MRI data as an outcome measure. That work takes advantage of some of the most powerful biomedical magnets in the world through the Advanced Magnetic Resonance Imaging and Spectroscopy facility located within the McKnight Brain Institute. Dr. Vaillancourt also uses advanced neuroimaging techniques to study the functional and structural changes in the brain of humans and animal models that span Parkinson’s disease, tremor, ataxia, and dystonia. Dr. Ferris and his group are pioneering the use of high-density electroencephalography (EEG) to perform mobile brain imaging with high temporal resolution. This last effort includes both new hardware and software innovations to facilitate removal of motion and muscle artifacts from EEG during walking and running.
Spinal cord injury (SCI) and neuromuscular plasticity
A well-integrated group of scientists with expertise in animal models and clinical research study neuromuscular plasticity following SCI. Neuroscientists (Drs. Mitchell, Fuller, and Dale), biomedical engineer Dr. Schmidt and neurological physical therapy experts (Drs. Fox and Gonzalez-Rothi) investigate locomotor training, electrical stimulation, pharmacological strategies, and oxygen manipulation as tools to promote functional recovery after SCI. Parallel studies are pursued in clinically-relevant rodent models and persons with incomplete SCI. As one example, Drs. Mitchell, Fuller and Gonzalez-Rothi have collaborated on preclinical studies showing that mild hypoxia triggers spinal neuroplasticity and recovery in rats with SCI. Building on this preclinical foundation, Dr. Fox has obtained research grants from the US Department of Defense to study intermittent hypoxia as a rehabilitation modality in humans with SCI. This type of collaboration and synergy illustrates the strength of our SCI group.
Engineering, technology and rehabilitation
Our T32 faculty includes engineers conducting rehabilitation-related research including Drs. Ferris, Schmidt, and Gundez. A common theme of their work is “restoration of human movement through technology”. Dr. Ferris’ program emphasizes human-machine interactions, mechanically and electrically. Dr. Schmidt’s research focuses on engineering novel materials and therapeutic systems to stimulate damaged peripheral and spinal neurons to regenerate. Dr Gundez’ work focuses on deep brain stimulation to improve motor control in humans with movement disorders.
Mechanisms of neuroplasticity: implications for rehabilitation
A group of McKnight Brain Institute neuroscientists study fundamental mechanisms of neuroplasticity and apply lessons learned toward development of therapeutic options (Drs. Bizon, Gonzalez-Rothi, Mitchell and Fuller). For example, Drs. Mitchell and Gonzalez-Rothi are exploring neuronal signaling pathways associated with spinal motor plasticity. Ongoing work is aimed at developing preconditioning strategies to boost the impact of conventional rehabilitation approaches for motor dysfunction. Dr. Mitchell’s work, describing how spinal serotonin receptor activation activates motor neuron signaling cascades, has led to ongoing initial clinical trials in persons with spinal cord injury. Collectively, the group aim is harnessing neuroplasticity to promote recovery and improve motor function in clinical conditions, and has expertise in molecular mechanisms through clinical testing. Research tools used include pharmacologic agents to enhance neuroplasticity, electrical stimulation in animal models and humans (e.g., transcutaneous direct current stimulation), gene transfer, and preconditioning modalities such as e-stim or mild hypoxia.