Kathryn J. Swoboda, MD
Dr. Swoboda received her medical degree at The Northwestern Feinberg School of Medicine. She completed her neurology residency at the Harvard Longwood Neurology Program at the Brigham and Women’s Hospital, and additional subspecialty training in Clinical Genetics and Neuromuscular disease/ Neurophysiology at Boston Children’s Hospital and the Lahey-Hitchcock Clinic. Dr. Swoboda’s research and clinical activities are dedicated to the diagnosis and treatment of neurologic disorders, especially neuromuscular diseases, movement disorders, and neurodegenerative disorders with childhood-onset.
Questions being addressed in the lab
- Do non-neural, systemic tissues contribute to Spinal Muscular Atrophy (SMA) pathology?
- What clinical, genetic, and molecular tools can predict the age of onset, disease severity and course of pathogenesis for rare neurogenetic diseases?
- What tissues, proteins, and molecular pathways can be targets of potential novel or co-adjuvant therapeutics for children and adults with neurogenetic diseases?
Projects underway to answer these questions
Neural and Non-Neural Contributions to Spinal Muscular Atrophy: A Human Tissue Study. Dr. Swoboda’s Lab Research Flow Chart. This illustration was created using templates from Servier Medical Art (https://smart.servier.com) licensed under a Creative Commons Attribution 3.0 Unported License
Figure 2. We examined a cohort of 238 patients with SMA with 1,130 creatinine (Crn) observations. Decreased Crn levels reflected disease severity, suggesting that Crn is a candidate biomarker for SMA progression. We conclude that Crn measurements should be included in the routine analysis of all patients with SMA. In future studies, it will be important to determine whether Crn levels respond to molecular and gene therapies.
Reference: Alves et al., Neurology, 2020; 94:1-11. DOI: 10.1212/WNL.0000000000008762
Figure 3: We identified a de novo missense mutation in NALCN, c.1768C.T, in an infant with a severe neonatal lethal form of the recently characterized CLIFAHDD syndrome (congenital contractures of the limbs and face with hypotonia and developmental delay). When engineered into the C elegans ortholog, this mutation results in a severe gain-of-function phenotype, with hypercontraction and uncoordinated movement.
Reference: Bend et al., Neurology, 2016; 87(11):1131-9. DOI: 10.1212/WNL.0000000000003095
Figure 4. Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2 recurrent mutations, D801N and E815K, and a more severe phenotype in the E815K cohort. We performed mutation analysis and retrospective genotype-phenotype correlations in all eligible patients with AHC enrolled in the US AHC Foundation registry from 1997-2012. We identified heterozygous ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31 (91%) are missense, and 16 (47%) had not been previously reported.
References: Viollet et al., PLoS One, 2015; 10(5):e0127045. DOI: 10.1371/journal.pone.0127045
Heinzen et al., Nat Genet. 2012; 44(9):1030-4. DOI: 10.1038/ng.2358