Maria Teresa Acosta, M.D.
NIH Undiagnosed Diseases Program
NHGRI-UDP-GM1 Gene Therapy Clinical Trial
M.D. Universidad Industrial de Santander (Bucaramanga, Colombia)
Biography
Dr. Acosta is a board-certified pediatric neurologist, originally from Colombia. She has additional training in pediatric neurophysiology and pediatric neuropsychology in Spain and the Netherlands, respectively. In 2000, she moved to the United States and completed her residency and fellowship training at Children’s National Hospital/George Washington University, including a fellowship training at NINDS/NIH in Epilepsy and animal models through 2005. Since 2005-2018, she worked as an attending physician at Children's National Hospital, as the Clinical Director of the Neurofibromatosis type 1 (NF1) Program and as an associate professor at George Washington University’s medical school. Through an IPA agreement, she worked during the same period as a medical director of the “Genetic Analysis of Attention Deficit Hyperactivity Disorder” (00-HG-0058) Medical Genetic Branch/NHGRI. In 2018, she accepted a full-time position as a pediatric neurologist at the NIH Undiagnosed Disease Program (UDP) and the GM1 gene therapy program led by Dr. Cynthia Tifft.
Scientific Summary
Her main area of professional interest is in the clinical and translational research of neurodevelopmental disabilities, from common conditions like ADHD to rare diseases like GM1 and the variety of conditions seen in the UDP. Her clinical research, initially in ADHD, then in NF1, combined detailed and extensive phenotype evaluations, neurodevelopmental assessments, the search for genetic and biological markers, and traditional and novel neuroimaging techniques to study a wide range of neurodevelopmental disabilities. This included research using MRS (Magnetic Resonance Spectroscopy) in the search for biological markers to predict the severity of ADHD in a subset of patients, to the creation of a translational model to test pharmacological and non-pharmacological interventions in animal models and NF1 patients using interspecies comparisons of clinical outcomes and brain connectivity changes using r-fMRI techniques. As associated investigator and a pediatric neurologist with the GM1 gene therapy trial, she is applying this background by assessing the impact of our intervention using traditional and novel techniques in brain MRI- including structural, magnetic resonance spectroscopy (MRS), resting-functional MRI (r-fMRI) and the very novel differential tractography (DT). This last one, DT, has so far shown the strongest results in differentiating treated, untreated patients and normal controls regarding changes in neural fibers over time.
She is an associated investigator for several natural history protocols at NIH: “Natural History Study of Children and Adults With Medullary Thyroid Cancer” (NCI 12-C-0178) ; “Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies” (NCI 20-C-0107); “Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome” (NCT02461420); and the “Autoimmune Brain Disorders Program” lead by Dr. Gena Mooneyham at NIMH.
Her current work exploring potential clinical outcomes and biomarkers using traditional and novel MRI techniques that may inform Clinical Outcome Assessments (COAS) or treatment responses is very promising. Current results using DT as part of the assessment of patients from the gene therapy GM1 protocol are strong and encouraging of the positive impact that the gene therapy may have on brain regeneration. This is especially significant, as some therapeutic interventions like gene therapy may not demonstrate meaningful clinical improvements in the short term. Validation in larger samples of the neurotypical population is on-going to better understand the biological underpins of brain development. Long-term, the use of these complex MRI techniques and methodological adaptations for very small clinical trials will advance the access and evaluation of therapeutic options that may come to ultra-small samples of patients, like those the UDP program serves.
Publications
Zaragoza Domingo S, Alonso J, Ferrer M, Acosta MT, Alphs L, Annas P, Balabanov P, Berger AK, Bishop KI, Butlen-Ducuing F, Dorffner G, Edgar C, de Gracia Blanco M, Harel B, Harrison J, Horan WP, Jaeger J, Kottner J, Pinkham A, Tinoco D, Vance M, Yavorsky C. Methods for Neuroscience Drug Development: Guidance on Standardization of the Process for Defining Clinical Outcome Strategies in Clinical Trials. Eur Neuropsychopharmacol. 2024 Jun;83:32-42. doi: 10.1016/j.euroneuro.2024.02.009. Epub 2024 Apr 4.
D'Souza P, Farmer C, Johnston J, Han ST, Adams D, Hartman AL, Zein W, Huryn LA, Solomon B, King K, Jordan C, Myles J, Nicoli ER, Rothermel CE, Algarin YM, Huang R, Quimby R, Zainab M, Bowden S, Acosta MT, Crowell A, Buckley A, Brewer C, Regier D, Brooks B, Baker E, Vézina G, Thurm A, Tifft CJ. GM1 Gangliosidosis Type II: Results of a 10-Year Prospective Study. medRxiv [Preprint]. 2024 Jan 4:2024.01.04.24300778. doi: 10.1101/2024.01.04.24300778. Update in: Genet Med. 2024 Jul;26(7):101144. doi: 10.1016/j.gim.2024.101144.
Pandina GJ, Busner J, Kempf L, Fallon J, Alphs LD, Acosta MT, Berger AK, Day S, Dunn J, Villalta-Gil V, Grabb MC, Horrigan JP, Jacobson W, Kando JC, Macek TA, Singh MK, Stanford AD, Domingo SZ. Ensuring Stakeholder Feedback in the Design and Conduct of Clinical Trials for Rare Diseases: ISCTM Position Paper of the Orphan Disease Working Group. Innov Clin Neurosci. 2024 Mar 1;21(1-3):52-60. eCollection 2024 Jan-Mar
Macnamara EF, Loydpierson A, Latour YL, D'Souza P, Murphy J, Wolfe L, Estwick T, Johnston JM, Yang J; Undiagnosed Diseases Network; Acosta MT, Lee PR, Pierson TM, Soldatos A, Toro C, Markello T, Adams DR, Gahl WA, Yousef M, Tifft CJ. Risks and benefits of anesthesia for combined pediatric procedures in the NIH undiagnosed diseases program. Mol Genet Metab. 2023 Nov;140(3):107707. doi: 10.1016/j.ymgme.2023.107707. Epub 2023 Oct 10.
Morimoto M, Bhambhani V, Gazzaz N, Davids M, Sathiyaseelan P, Macnamara EF, Lange J, Lehman A, Zerfas PM, Murphy JL, Acosta MT, Wang C, Alderman E; Undiagnosed Diseases Network; Reichert S, Thurm A, Adams DR, Introne WJ, Gorski SM, Boerkoel CF, Gahl WA, Tifft CJ, Malicdan MCV. Bi-allelic ATG4D variants are associated with a neurodevelopmental disorder characterized by speech and motor impairment. NPJ Genom Med. 2023 Feb 10;8(1):4. doi: 10.1038/s41525-022-00343-8.
Nicoli ER, Huebecker M, Han ST, Garcia K, Munasinghe J, Lizak M, Latour Y, Yoon R, Glase B, Tyrlik M, Peiravi M, Springer D, Baker EH, Priestman D, Sidhu R, Kell P, Jiang X, Kolstad J, Kuhn AL, Shazeeb MS, Acosta MT, Proia RL, Platt FM, Tifft CJ. Glb1 knockout mouse model shares natural history with type II GM1 gangliosidosis patients. Mol Genet Metab. 2023 Feb;138(2):107508. doi: 10.1016/j.ymgme.2023.107508. Epub 2023 Jan 13.
Busner J, Pandina G, Domingo S, Berger AK, Acosta MT, Fisseha N, Horrigan J, Ivkovic J, Jacobson W, Revicki D, Villalta-Gil V. Clinician- and Patient-reported Endpoints in CNS Orphan Drug Clinical Trials: ISCTM Position Paper on Best Practices for Endpoint Selection, Validation, Training, and Standardization. Innov Clin Neurosci. 2021 Oct-Dec;18(10-12):15-22.
Hardy KK, Berger C, Griffin D, Walsh KS, Sharkey CM, Weisman H, Gioia A, Packer RJ, Acosta MT. Computerized Working Memory Training for Children With Neurofibromatosis Type 1 (NF1): A Pilot Study. J Child Neurol. 2021 Oct;36(12):1078-1085. doi: 10.1177/08830738211038083. Epub 2021 Sep 2.
Kaczorowski JA, Smith TF, Shrewsbury AM, Thomas LR, Knopik VS, Acosta MT. Neurofibromatosis Type 1 Implicates Ras Pathways in the Genetic Architecture of Neurodevelopmental Disorders. Behav Genet. 2020 Jul;50(4):191-202. doi: 10.1007/s10519-020-09991-x. Epub 2020 Feb 5.
Payne JM, Hearps SJC, Walsh KS, Paltin I, Barton B, Ullrich NJ, Haebich KM, Coghill D, Gioia GA, Cantor A, Cutter G, Tonsgard JH, Viskochil D, Rey-Casserly C, Schorry EK, Ackerson JD, Klesse L, Fisher MJ, Gutmann DH, Rosser T, Packer RJ, Korf B, Acosta MT, North KN; NF Clinical Trials Consortium. Reproducibility of cognitive endpoints in clinical trials: lessons from neurofibromatosis type 1. Ann Clin Transl Neurol. 2019 Dec;6(12):2555-2565. doi: 10.1002/acn3.50952. Epub 2019 Dec 3.
Kruszka P, Buscetta A, Acosta MT, Banks N, Addissie YA, Toro C, Luby M, Latour L, Vezina G, Page DC, Muenke M. Circle of Willis anomalies in Turner syndrome: Absent A1 segment of the anterior cerebral artery. Birth Defects Res. 2019 Nov 15;111(19):1584-1588. doi: 10.1002/bdr2.1609. Epub 2019 Oct 18.
Shofty B, Bergmann E, Zur G, Asleh J, Bosak N, Kavushansky A, Castellanos FX, Ben-Sira L, Packer RJ, Vezina GL, Constantini S, Acosta MT, Kahn I. Autism-associated Nf1 deficiency disrupts corticocortical and corticostriatal functional connectivity in human and mouse. Neurobiol Dis. 2019 May 22;130:104479. doi: 10.1016/j.nbd.2019.104479.
Yoncheva YN, Hardy KK, Lurie DJ, Somandepalli K, Yang L, Vezina G, Kadom N, Packer RJ, Milham MP, Castellanos FX, Acosta MT. Computerized cognitive training for children with neurofibromatosis type 1: A pilot resting-state fMRI study. Psychiatry Res Neuroimaging. 2017 Aug 30;266:53-58. doi: 10.1016/j.pscychresns.2017.06.003. Epub 2017 Jun 6.
Payne JM, Barton B, Ullrich NJ, Cantor A, Hearps SJ, Cutter G, Rosser T, Walsh KS, Gioia GA, Wolters PL, Tonsgard J, Schorry E, Viskochil D, Klesse L, Fisher M, Gutmann DH, Silva AJ, Hunter SJ, Rey-Casserly C, Cantor NL, Byars AW, Stavinoha PL, Ackerson JD, Armstrong CL, Isenberg J, O'Neil SH, Packer RJ, Korf B, Acosta MT, North KN; NF Clinical Trials Consortium. Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1. Neurology. 2016 Dec 13;87(24):2575-2584. doi: 10.1212/WNL.0000000000003435. Epub 2016 Nov 9.
Morris SM, Acosta MT, Garg S, Green J, Huson S, Legius E, North KN, Payne JM, Plasschaert E, Frazier TW, Weiss LA, Zhang Y, Gutmann DH, Constantino JN. Disease Burden and Symptom Structure of Autism in Neurofibromatosis Type 1: A Study of the International NF1-ASD Consortium Team (INFACT). JAMA Psychiatry. 2016 Dec 1;73(12):1276-1284. doi: 10.1001/jamapsychiatry.2016.2600.
Martinez AF, Abe Y, Hong S, Molyneux K, Yarnell D, Löhr H, Driever W, Acosta MT, Arcos-Burgos M, Muenke M. An Ultraconserved Brain-Specific Enhancer Within ADGRL3 (LPHN3) Underpins Attention-Deficit/Hyperactivity Disorder Susceptibility. Biol Psychiatry. 2016 Dec 15;80(12):943-954. doi: 10.1016/j.biopsych.2016.06.026. Epub 2016 Jul 14.
Acosta MT. Searching for molecular-targeted interventions for NF1 cognitive deficits in the classroom. Dev Med Child Neurol. 2015 Dec;57(12):1088-9. doi: 10.1111/dmcn.12792. Epub 2015 Apr 28.
Kadom N, Nai N, Udyavar R, Noor A, Packer R, Vezina G, Acosta MT. Cingulate Apparent Diffusion Coefficient measurements in children with Neurofibromatosis type 1. J Pediatr Neuroradiol. 2014; 03(03):121-124.
Acosta MT. Challenges of cognitive research in neurofibromatosis type 1. Lancet Neurol. 2013 Nov;12(11):1040-1. doi: 10.1016/S1474-4422(13)70179-0. Epub 2013 Oct 7.
Walsh KS, Vélez JI, Kardel PG, Imas DM, Muenke M, Packer RJ, Castellanos FX, Acosta MT. Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1. Dev Med Child Neurol. 2013 Feb;55(2):131-138. doi: 10.1111/dmcn.12038. Epub 2012 Nov 16.
Arcos-Burgos M, Londoño AC, Pineda DA, Lopera F, Palacio JD, Arbelaez A, Acosta MT, Vélez JI, Castellanos FX, Muenke M. Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls. Atten Defic Hyperact Disord. 2012 Dec;4(4):205-12. doi: 10.1007/s12402-012-0088-0. Epub 2012 Jul 20.
Chabernaud C, Mennes M, Kardel PG, Gaillard WD, Kalbfleisch ML, Vanmeter JW, Packer RJ, Milham MP, Castellanos FX, Acosta MT. Lovastatin regulates brain spontaneous low-frequency brain activity in neurofibromatosis type 1. Neurosci Lett. 2012 Apr 25;515(1):28-33. doi: 10.1016/j.neulet.2012.03.009. Epub 2012 Mar 13.
Acosta MT, Kardel PG, Walsh KS, Rosenbaum KN, Gioia GA, Packer RJ. Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: phase I study. Pediatr Neurol. 2011 Oct;45(4):241-5. doi: 10.1016/j.pediatrneurol.2011.06.016.
Acosta MT, Munashinge J, Zhang L, Guerron DA, Vortmeyer A, Theodore WH. Isolated seizures in rats do not cause neuronal injury. Acta Neurol Scand. 2012 Jan;125(1):30-7. doi: 10.1111/j.1600-0404.2011.01521.x. Epub 2011 May 26.
Lorenzo J, Barton B, Acosta MT, North K. Mental, motor, and language development of toddlers with neurofibromatosis type 1. J Pediatr. 2011 Apr;158(4):660-5. doi: 10.1016/j.jpeds.2010.10.001. Epub 2010 Nov 20.
Acosta MT, Munasinghe J, Pearl PL, Gupta M, Finegersh A, Gibson KM, Theodore WH. Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency. J Child Neurol. 2010 Dec;25(12):1457-61. doi: 10.1177/0883073810368137. Epub 2010 May 5.
Arcos-Burgos M, Jain M, Acosta MT, Shively S, Stanescu H, Wallis D, Domené S, Vélez JI, Karkera JD, Balog J, Berg K, Kleta R, Gahl WA, Roessler E, Long R, Lie J, Pineda D, Londoño AC, Palacio JD, Arbelaez A, Lopera F, Elia J, Hakonarson H, Johansson S, Knappskog PM, Haavik J, Ribases M, Cormand B, Bayes M, Casas M, Ramos-Quiroga JA, Hervas A, Maher BS, Faraone SV, Seitz C, Freitag CM, Palmason H, Meyer J, Romanos M, Walitza S, Hemminger U, Warnke A, Romanos J, Renner T, Jacob C, Lesch KP, Swanson J, Vortmeyer A, Bailey-Wilson JE, Castellanos FX, Muenke M. A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol Psychiatry. 2010 Nov;15(11):1053-66. doi: 10.1038/mp.2010.6. Epub 2010 Feb 16. PMID: 20157310.
Munasinghe JP, Banerjee M, Acosta MT, Banks M, Heffer A, Silva AC, Koretsky A, Theodore WH. Arterial spin labeling demonstrates that focal amygdalar glutamatergic agonist infusion leads to rapid diffuse cerebral activation. Acta Neurol Scand. 2010 Mar;121(3):209-16. doi: 10.1111/j.1600-0404.2009.01188.x. Epub 2009 Nov 25.
Acosta MT, Castellanos FX, Bolton KL, Balog JZ, Eagen P, Nee L, Jones J, Palacio L, Sarampote C, Russell HF, Berg K, Arcos-Burgos M, Muenke M. Latent class subtyping of attention-deficit/hyperactivity disorder and comorbid conditions. J Am Acad Child Adolesc Psychiatry. 2008 Jul;47(7):797-807. doi: 10.1097/CHI.0b013e318173f70b.
Last updated: July 21, 2024