Nervous System Diseases

Burghes Laboratory

The Burghes Laboratory focuses on understanding genetic neuromuscular disorders on a molecular level. In particular, they are unraveling the molecular biology of spinal muscular atrophy (SMA). SMA is an autosomal recessive disorder that is characterized by destruction of motor neurons in the anterior horn of the spinal cord. The disorder is typically classified into three types based on clinical severity. SMA is caused by loss or mutation of the SMN1 gene, while the virtually identical SMN2 gene remains unmodified. The two genes essentially differ by a single nucleotide that affects the incorporation of exon 7 into the SMN message. As a result of this change in SM1, the SMN2 gene produces insufficient SMN protein for motor neurons. SMN supports the biogenesis of small nuclear ribonucleic proteins (snRNPs), which are essential for all cells. Currently it is not clear why high SMN levels are so critically important for motor neurons.

The researchers have developed a mouse model of SMA, which has shown that high copy number of the SMN2 gene can rescue the SMA mouse. They are using this model of SMA to understand why motor neurons are affected and to develop treatments for SMA. They are also using high throughput screening to look for compounds that can activate SMN, in the hope of finding new therapies for SMA.

The lab is also developing methods for treating Duchenne muscular dystrophy (DMD) using gene therapy. DMD is a muscle wasting disorder caused by mutations in the large dystrophin gene. They are particularly interested in strategies that take use the adeno associated virus vector to deliver for gene therapy.

Lonser Laboratory

Dr. Russell Lonser's laboratory is a translational neuroscience group. They have developed several clinical programs based on MR-guided delivery of gene therapy and their translational efforts led to the initiation of four clinical trials in different neurological disorders (Parkinson’s disease and AADC deficiency) and brain tumors (brain stem glioma and glioblastoma). Currently, they are also developing new treatments for adult and pediatric neurologic and neurodevelopmental disorders such as Alzheimer’s disease, Huntington’s disease, multiple system atrophy and lysosomal storage disorders as well as for substance abuse disorders. As a part of the overall gene therapy platform, they’ve also developed devices and procedures to advance intracranial AAV-based gene therapies, cell therapies and drug delivery for neurological disorders and brain cancer for first-in-human clinical trials.

As a Research Scientist in the Lonser Lab, Dr. Jerusha Naidoo’s research is focused on developing novel gene therapies for sensorineural hearing loss, the most common sensory disorder in humans. Specifically, she develops gene therapies targeted to auditory nerves for the treatment of hearing loss due to noise exposure, infection, and ototoxic drug exposure. The majority of gene therapy approaches for sensorineural neural hearing loss have focused primarily on gene delivery to the hair cells (the sensory cells in the ear). Although the inner ear is typically considered to be a closed system – the health and integrity of spiral ganglion neurons are also important to maintain to allow perception of sound.

Dr. Naidoo undertook her postdoctoral training under the supervision of Dr. Krystof Bankiewicz, a leader in the gene therapy field in the translational and clinical development gene therapies for neurological disorders. Dr. Naidoo collaborates with Dr. Yin Ren (Department of Otolaryngology) and Dr. Eric Bielefeld (Department of Speech and Hearing Science).

As a Research Scientist in the Lonser Lab, Dr. Victor Van Laar’s research focuses on understanding the role of mitochondrial dysfunction, cellular bioenergetics, and neuronal homeostasis in neurodegenerative diseases and other neurologically related disorders, including Parkinson’s disease, substance abuse, and depression. His research utilizes rodent models to better understand why these neurological conditions develop and how they might be treated. By developing and utilizing novel approaches for the delivery of therapeutic agents to target specific regions in the brain, Dr. Van Laar is also exploring gene therapy approaches to treating these brain disorders. Gene transfer and gene editing therapeutic approaches in the brain are evaluated by a combination of behavioral assessments and biochemical assays to evaluate efficacy. Techniques including immunohistochemistry, microscopy, quantitative image analyses, HPLC, and protein chemistry are utilized to assess the translational relevance of potential gene therapies.

Herson Laboratory

Dr. Herson’s research focuses on understanding mechanisms of injury and repair following ischemic brain injury, with studies related to ion channels/receptors, neuroinflammation, age and gender. Current studies are focused on the impact of ischemia on synaptic function and plasticity with the goal of revealing pharmacological interventions that both prevent acute ischemic injury and improve long-term brain function after injury. He received several NIH, DoD and AHA grants and has been continuously NIH funded throughout his independent career. Dr. Herson has published over 100 peer reviewer articles, developed multiple patents and mentored several junior faculty, both PhD and clinician-scientists.

Kolb Laboratory

The Kolb Lab is devoted to the understanding of molecular pathways that, when altered, result in diseases of the motor neuron. They are particularly interested in alterations in RNA metabolism that result in neurological diseases. The molecular mechanisms of spinal muscular atrophy and of amyotrophic lateral sclerosis (ALS) are current foci for biochemical and cell-based investigation. Their long-term goals are to determine the precise mechanisms that cause motor neuron diseases, including sporadic amyotrophic lateral sclerosis, and to develop small molecule and/or gene-based therapies for these diseases.

Orfila Laboratory

The Orfila laboratory focuses on understanding mechanisms of injury and repair following Traumatic brain injury (TBI), a leading cause of mortality and morbidity in adults, with significant sequelae including memory deficits.  Despite intense research, no pharmacological interventions are currently available to improve functional recovery following TBI.  The Orfila lab currently investigates the effects of TBI on memory acquisition and retrieval in a gender and age dependent manner.  Through electrophysiological, behavioral and molecular methods, these studies focus on investigating the important cellular mechanisms underlying impaired hippocampal function, an area known for memory storage and retrieval.  To advance their findings from mechanism to translation, they are using viral-mediated gene therapy as therapeutic strategies targeting pathways identified in their basic animal studies.

Ren Laboratory

Yin Ren, MD PhD is a surgeon-scientist and an Assistant Professor in the Department of Otolaryngology . The Ren laboratory focuses on understanding the mechanism of tumor growth and extracellular matrix remodeling in diseases of the nervous system, particularly tumors of the cranial base such as vestibular schwannoma. Despite tremendous disease morbidity, no FDA-approved pharmacotherapies currently exist. Using cellular and animal models and tumor samples from patients undergoing surgery, the lab investigates molecular mechanisms underlying cellular proliferation and symptoms such as hearing loss. The laboratory is also developing nanotechnology-based tools to improve the diagnosis and targeted treatment of these tumors. Finally, in collaboration with investigators at the GTI and NCH, they are investigating AAV-mediated gene therapy as a therapeutic strategy for vestibular schwannoma and Neurofibromatosis Type 2.  Dr. Ren also takes care of patients with hearing loss and skull base tumors at The Ohio State University Wexner Medical Center.

Samaranch Laboratory

At the Samaranch Laboratory, we are committed to developing cutting-edge gene therapies for inherited disorders using recombinant AAV-based technology. Our core strength lies in the precise direct delivery of therapeutic agents into the central nervous system. We use stereotactic and microsurgical techniques, including intracranial convection-enhanced delivery, cerebrospinal fluid injections, and in-utero gene transfer. Our research includes capsid development, cell targeting and axonal transport optimization, and immune response assessment to provide disease-specific gene transfer needed to maximize the efficacy and safety of these treatments.

Our current preclinical studies include the therapeutic development for lysosomal storage disorders (Niemann-Pick Type A and GM1 gangliosidosis), neurotransmitter-related diseases (AADC and MAO deficiencies), and neurodegenerative diseases (Parkinson's and Alzheimer's diseases). 

Townsend Laboratory

The Townsend Lab for Neurobiology & Energy Balance investigates how the nervous system (brain and peripheral nerves) regulate appetite, energy expenditure, and metabolic health.  To do this, we take a broad physiological approach ranging from basic neurobiology to translational/clinical experimentation, encompassing neuroscience, cell and molecular biology, biochemistry, and metabolic physiology approaches using cell culture, mouse transgenic models, and human tissue samples.  Lab projects fall in two areas of focus: 1) brain/hypothalamic adult stem cells and neural plasticity in the regulation of energy balance homeostasis; and 2) brain-adipose neural communication and adipose innervation by sensory and sympathetic nerves, including neurovascular and neuroimmune interactions, neurotrophic factor action, and adipose neural plasticity and neuropathy.  Our research program impacts the study of obesity, diabetes, cardiovascular disease, cancer, and aging.  Gene therapy projects include targeting peripheral nerves, adipose tissue, and the hypothalamus in the improvement of metabolic health and neural plasticity/remodeling.

As a Research Scientist in the Townsend lab, Dr. Magdalena Blaszkiewicz’s research program focuses on adipose neuropathy and potential gene therapy treatments, as well as neuroimmune interactions in the maintenance and control of adipose axonal health and plasticity. Her future independent research will focus on investigating how lymphatic vessels and lymph nodes in adipose serve as a nexus of neuroimmune cell crosstalk. A goal of this research is to determine if and how loss of nerves around lymphatic vasculature and lymph nodes in adipose tissues affect immune cell functions and trafficking, as well as fluid homeostasis in health and disease.