Child Neurology Research

Division of Child Neurology faculty conducts a variety of neurologic bench/basic research and clinical studies, including clinical trials. Current studies are focused on the following areas:

• Gene therapy
• Movement disorders
• Metabolic disorders of the nervous system
• Neuromuscular disease clinical trials
• Anti-epileptic drug trials
• Clinical trials in pediatric stroke
• Clinical studies on the autism spectrum
• Concussion recovery utilizing cerebrovascular functioning

Faculty research projects:

• Berge Minassian, M.D.

  Dr. Minassian is an international authority on Lafora disease, a glycogen storage disorder of the brain with intractable and fatal epilepsy. His laboratory has uncovered large amounts of knowledge on the metabolism of glycogen in the brain.

  In addition, he is building the premier national Gene Therapy Center with his colleague Steven J. Gray, Ph.D., and others on the faculty. The goal is a complete transformation of pediatric neurology whereby children with single-gene-defect brain diseases, as appropriate, would receive treatment in the form of replacing the missing gene.

• Dallas Armstrong, M.D.

  Dr. Armstrong is involved in several projects related to Rett syndrome. She is the Medical Director of the Rett Syndrome and Related Disorders Clinic, which received a Center of Excellence (CoE) designation in 2021 from the International Rett Syndrome Foundation (IRSF), and participates in an ongoing patient registry study, for which the clinic received a grant in 2021.

  Dr. Armstrong works with Hoang Nguyen, M.D., in the Division of Pediatric Cardiology, as well as neurology trainees on projects related to cardiac electrophysiology in girls and women with Rett syndrome and with medical students on the caregiver burden in boys with severe neonatal encephalopathy related to MECP2. She is working with several colleagues at Rett CoEs across the country on an original research project investigating anti-seizure medication use and efficacy in the Natural History Database, as well as on a revision of the clinical practice guidelines in Rett syndrome.

  Dr. Armstrong serves on the IRSF medical advisory board and clinical trial committee. She also works with Dr. Sirsi and resident trainees on projects related to TBC1D24 epileptic encephalopathy. Lastly, Dr. Armstrong is working with a neurology trainee as well as colleagues across institutions on a seizure semiology smartphone application.

• Xin Chen, M.D.

  Dr. Chen is the principal investigator (PI) of three research projects (DDX3X, GNAO1, and CMT4A) initially funded by Taysha Gene Therapies and two new research projects (PDHA1 and LNPK) funded by primary foundations. He is also the Co-Investigator of multiple research projects funded by private foundations, industry, and the National Institutes of Health (NIH) under Dr. Gray.

  Dr. Chen’s other research areas are aspartylglucosaminuria (AGU), CLN7 Batten disease, SPG50 disease, SLC52A2 deficiency disease, and SRD5A3 deficiency disease. In 2021, an investigational new drug (IND) application to initiate a Phase I intrathecal gene transfer trial for AAV9/MFSD8 was approved by the U.S. Food and Drug Administration (FDA), and the trial is ongoing at Children’s Medical Center Dallas, in collaboration with UTSW (clinicaltrials.gov NCT04737460). In 2022, the IND application to initiate a Phase I intrathecal gene transfer trial for AAV9/AP4M1 was approved by the FDA, and the trial is enrolling SPG50 patients at Children’s Medical Center Dallas, in collaboration with UTSW (clinicaltrials.gov NCT05518188).

  He is currently working to facilitate the initiation of gene therapy clinical trials for AGU gene therapy. Dr. Chen is also helping to develop novel adeno-associated virus (AAV) capsids with superior efficacy, higher specificity, and less toxicity; supporting several projects in other laboratories and institutions; and mentoring laboratory personnel.

• Lauren N. Dengle Sanchez, M.D.

  Dr. Sanchez is involved in clinical research in the areas of rare neurogenetic disorders, neurometabolic disorders, and neuro-oncology.

• Michael M. Dowling, M.D., Ph.D., M.S.C.S.

  Dr. Dowling is involved in clinical research in the areas of stroke in children, Sturge-Weber syndrome, and neurologic complications of sickle cell disease.

• Wilmot Bonnet, M.D.

  Dr. Bonnet is involved in clinical research in the areas of ischemic and hemorrhagic stroke in children, acute interventions for ischemic stroke, and recovery in children with acquired brain injury.

• Patricia A. Evans, M.D., Ph.D.

  Dr. Evans is an active participant in translational research, both for autism spectrum disorders as well as fragile X syndrome. She participates in a range of studies, including the genetics of autism, spectrum disorders, and the mechanisms of fragile X syndrome cognitive deficits.

• Steven J. Gray, Ph.D.

  Dr. Gray is the PI on several grant-funded projects and sponsored research agreements. These include an NIH R01 grant to develop novel AAV capsids for central nervous system (CNS) gene transfer, an NIH R01 subcontract to develop a gene therapy approach for Niemann-Pick Type C disease, as well as foundation grants from the Cure SPG50 Foundation and the Sappani Foundation.

  He also has multiple sponsored research agreements from Taysha Gene Therapies, as well as sponsored research agreements from Roche, 3M, Millipore Sigma, Form Bio, Phoenix Nest, the Monoamine Oxidase Deficiency (MAO) Foundation, the Charcot-Marie-Tooth Association, the DDX3X Foundation (Co-PI), and Hannah’s Hope Fund. Dr. Gray has two well-scored pending NIH grants that initiated in 2023: U01 to initiate a trial for aspartylglucosaminuria and U19 for preclinical gene editing.

  His funded research projects include the development of gene therapy treatments for giant axonal neuropathy (GAN), CLN7 Batten disease, multiple sulfatase deficiency, Rett syndrome, Angelman syndrome, SLC6A1 deficiency, SPG50 disease, SLC52A2 disease, GNAO1, DDX3X, Charcot-Marie Tooth disease types 4A and 4J, fragile X syndrome, SRD5A3, non-ketonic hyperglycinemia, MAO deficiency, mucopolysaccharidosis type 3C, and Leigh syndrome.

  Dr. Gray created a core facility for research and clinical AAV manufacture and also facilitated the initiation of gene therapy clinical trials for multiple rare neurological diseases, including CLN7 Batten disease and spastic paraplegia type 50 at UTSW and the following disorders elsewhere: GAN, CLN1 Batten disease, CLN5 Batten disease, Rett syndrome, and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases). He's had seven publications since the start of 2022, including two recent ones of note in the Journal of Clinical Investigation (Chen X et al., 2022; Chen X et al., 2023).

• Sharmistha Mitra, Ph.D.

  Dr. Mitra is an NIH-NINDS-funded principal investigator in the Division who studies mechanistic pathways of pediatric metabolic diseases, where glycogen metabolism is dysregulated. The Mitra Lab at UT Southwestern is especially interested in identifying the role of cellular ubiquitination pathways in metabolic neurodegenerative conditions. Dr. Mitra is also a co-investigator of the multi-PI Chan Zuckerberg Initiative, a funded grant (PI: Dr. Minassian) to investigate the molecular mechanism of Lafora disease.

  Throughout her research career at UT Southwestern, Dr. Mitra has been awarded several research awards that include the Wellstone Foundation Award, the Small Animal Center Research Award, and the American Society for Investigative Pathology Summer Project Award to decipher the role of protein ubiquitination in glycogen metabolism. While her primary research interests are ubiquitination in glycogen metabolism and related neuromuscular diseases, her lab frequently collaborates with other clinical scientists in the Division and abroad to develop targeted molecular therapy for metabolic neuromuscular diseases.

• Susan T. Iannaccone, M.D.

  Dr. Iannaccone is Director of Clinical Research for the Division of Child Neurology. Since 2015, she has been Associate Director of the UTSW Wellstone Muscular Dystrophy Cooperative Research Center, funded by the NIH and led by Eric Olson, Ph.D., and Co-Chair of the Administrative Core for the Wellstone Center.

  She serves on research grant review committees as well as several planning committees and panels for patient groups and the NIH. She trained/mentored more than 20 pediatric neuromuscular fellows and medical students. Dr. Iannaccone is the site PI or site Co-PI for more than a dozen industry-sponsored clinical trials for pediatric neuromuscular and neurodegenerative diseases, including gene therapy and first-in-human trials.

  She is currently working with the UTSW Gene Therapy Program as a mentor for early-stage clinical investigators as part of the team performing investigational new drug (IND) applications. She is PI or Co-PI for human trials, including:

  • A Phase I/II Open-Label Intrathecal Administration of MELPIDA to Determine the Safety and Efficacy for Patients with Spastic Paraplegia Type 50 (SPG50) Caused by a Mutation in the AP4M1 Gene (active)
  • A Phase 1/2 Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Intravenous RGX-202 Gene Therapy in Males with Duchenne Muscular Dystrophy (DMD) (active)
  • A Phase I Intrathecal Lumbar Administration of AAV9/CLN7 for Treatment of CLN7 Disease (active)
  • Development of early metabolic imaging biomarkers for muscular dystrophy and cardiomyopathy in patients (active, PI Park)
  • A Prospective Natural History and Outcome Measure Discovery Study of Charcot-Marie-Tooth Disease, Type 4J (active)
• Saima Kayani, M.D.

  Dr. Kayani has been actively involved in the development of clinical aspects of gene therapy trials at UT Southwestern and serves as PI and Co-PI for NIH and industry-sponsored trials. These trials are ongoing at UT Southwestern/Children’s Medical Center Dallas, with other sponsored programs upcoming.

  Dr. Kayani has carried out various research responsibilities, including handling and writing informed consent documents, writing clinical protocols for the institutional review board (IRB), and overseeing and upholding medical ethics and regulatory issues. She has acted in the capacity of Lead Investigator and Medical Adviser and developed protocols, case report forms, and data capture platforms.

  Dr. Kayani has also been actively involved in the development of the clinical section of INDs for the first-in-human Phase I intrathecal gene therapy trial for Batten disease type 7 (CLN7). These efforts have led to the successful FDA approval of an open IND for a Phase I trial for intrathecal gene therapy in CLN7. As the Co-PI for the CLN7 Phase I first-in-human clinical trial, she is leading the clinical team in the successful implementation of the trial and overseeing all regulatory compliance.

  As a key opinion leader, Dr. Kayani has provided extensive clinical insight and strategic planning input, along with proficient clinical operations, to biotech companies such as Taysha Gene Therapies in partnership with the UTSW Gene Therapy Program. This involves regular standing weekly/monthly meetings discussing disease phenotypes, clinical impressions, experimental design, disease-specific biomarkers, and data analysis. These efforts have led to the start of a prospective natural history trial for the rare brain disease SURF1-related Leigh syndrome (starting in early 2022).

• Mathew Stokes, M.D.

  Dr. Stokes is involved in clinical research studies focused on biomarkers and phenotypes of concussion. He is the Children’s Medical Center Dallas site Principal Investigator for ConTex, which is a multicenter, prospective longitudinal registry for concussion established in 2015. Additionally, he is a Co-PI on a multicenter study, CARE4KIDS, looking at objective biomarkers of concussive head injury.

• Rana R. Said, M.D., F.A.A.N.

  Dr. Said is involved in multiple industry-sponsored clinical research trials. She is the PI for a study evaluating neonatal seizure detection algorithms (Cerebell). She is the principal PI and EEG reader for a multisite trial for pediatric dose optimization for EMS (PediDose; NIH). In addition, she is currently the Co-PI working with Dr. Sanchez, Daniel Bowers, M.D. (Pediatric Neuro-oncology), Evan Nock, M.D., Ph.D. (Adult Neuro-oncology), and Rebekah Clarke, M.D. (Neuroradiology), in an IRB-approved study to assess a strict classic ketogenic diet for recurrent or progressive refractory brain tumors in children.

  This is a prospective study to assess not only the response (anti-tumor effect on the ketogenic diet) but also the ability to achieve and maintain ketosis with a rigidly calculated and supervised classic ketogenic diet. The study will also assess biomarkers of efficacy by screening for the expression of enzymes that are critical for ketone metabolism in brain tumor samples. Magnetic response spectroscopy will also be utilized to evaluate the presence of certain metabolites in tumors that may serve as important biomarkers of tumor behavior and response to therapy.

  Dr. Said is also the PI of a study for the treatment of super refractory status epilepticus with tocilizumab versus anakinra (funding support, PCORI). She is involved with several medical education studies in conjunction with other members of the Education Committee of the American Academy of Neurology. She is also involved in clinical research on new-onset refractory status epilepticus and infantile spasms.

• Deepa Sirsi, M.D.

  Dr. Sirsi is involved in a range of clinical research studies concerning electroencephalograms (EEGs) as a predictor of neuroimaging and outcome in pediatric ECMO and pediatric nonaccidental head trauma; EEG biomarkers in single gene disorders such as GLUT1 deficiency syndrome; and SLC6A1 syndrome. She is the site PI for industry-funded anti-seizure medication trials.

  Dr. Sirsi collaborates with other clinicians and basic scientists in research involving treatment of the genetic causes of epilepsy and neurodevelopmental disorders. She participates in multicenter research studies on infantile spasms conducted by the Pediatric Epilepsy Research Consortium.

• Peter Tsai, M.D., Ph.D.

  Dr. Tsai directs the Cerebellar Neurodevelopmental Disorders Clinic and performs both pre-clinical and translational research for autism and neurodevelopmental disorders, including fragile X syndrome and tuberous sclerosis. He is the PI on numerous federally funded preclinical and translational research projects. These include NIH R01 and Department of Defense (DOD) grants to delineate circuit mechanisms underlying autism-relevant behaviors in tuberous sclerosis, an NIH R01 grant to explore the circuits contributing to abnormal behaviors in fragile X syndrome, and a DOD-funded grant examining brain mechanisms and the potential benefits of noninvasive brain stimulation for children with autism. He is actively working to develop therapeutic targets and examine the therapeutic efficacy of brain stimulation for children with neurodevelopmental disorders.

• Cynthia Wang, M.D.

  Dr. Wang is involved in clinical research characterizing demyelinating and other immune-mediated brain conditions, such as multiple sclerosis, neuromyelitis optica spectrum disorder, and autoimmune encephalitis in the pediatric population. She is the PI on two upcoming clinical trial studies on pediatric multiple sclerosis and neuromyelitis optica spectrum disorder. Dr. Wang has published original research and case reports/case series on unique patient presentations in the field of rare neuroimmunological disorders.

• Jeff Waugh, M.D., Ph.D.

  Dr. Waugh is involved in neuroimaging projects that utilize MRI to study the brain in patients with the movement disorder dystonia. In addition to these disease-related research projects, he develops novel methods for improving the accuracy of quantitative diffusion imaging and for identifying compartments within the human striatum in vivo that have previously been visualized only via post-mortem histology. Dr. Waugh collaborates with researchers and clinicians at the Harvard-MIT Martinos Center for Biomedical Imaging, Boston Children’s Hospital, Lübeck University in Germany, and the University of Santo Tomas and the University of the Philippines, both in Manila, Philippines. He has current grant funding from the NINDS, the Children's Clinical Research Advisory Committee, and the Brain and Behavior Research Foundation.

• Felix Nitschke, Ph.D.

  Dr. Nitschke is a PI investigating the metabolic pathways involved in several neurodegenerative diseases, such as Lafora disease and adult polyglucosan body disease. His work currently focuses on glycogen metabolism and the treatment of associated neurological diseases with novel gene therapy approaches. Dr. Nitschke received funding from the Orphan Disease Center at the University of Pennsylvania. In addition, he serves as Lead Investigator on a five-year grant from the NIH’s NINDS and as Co-PI on a collaborative grant from the Chan Zuckerberg Initiative.

• Mayank Verma, M.D., Ph.D.

  Dr. Verma is involved in preclinical and translational studies focusing on progressive myoclonic epilepsy and glycogen storage disorders. He is focusing on natural history studies and biomarkers with the end goal of developing the tools needed to effectively treat children with neurological diseases.