SMC1A Studies Around the World
Dr. Jeffrey Skolnick — Georgia Tech
- Area: Computational biology and protein modeling
- Uses AlphaFold and other protein-structure prediction approaches.
- SMC1A project: Modeling how individual SMC1A variants may alter protein structure and function.
- Goal: Help determine the likely biological consequences of different mutations.
Dr. Yong Cheng — Minzu University of China, Beijing
- Area: Translational neuroscience / pharmaceutical sciences
- Experience developing engineered exosomes.
- SMC1A project: Exploring an engineered exosome-based therapeutic approach.
- Goal: Develop a potential delivery/treatment strategy for SMC1A.
Dr. Xiao Mao — Xiangya Hospital, Central South University
- Area: SMC1A disease modeling and gene therapy
- Building a collection of patient-derived iPSC lines representing SMC1A loss-of-function variants.
- SMC1A project:
- Understand how heterozygous SMC1A LOF causes female-limited DEE, particularly refractory seizures, seizure clustering, and seizures that persist into older ages.
- Test the efficacy and safety of AAV9-mediated SMC1A gene compensation at the neuronal level.
- Use the mechanistic findings to identify additional therapeutic strategies.
Dr. Antonio Musio & Dr. Maddalena Di Nardo — National Research Council (CNR), Italy
(ongoing)
- Area: SMC1A molecular biology and cohesin
- Study how individual mutations affect SMC1A expression and protein function.
- SMC1A project: Mutation-specific functional studies and ataluren/readthrough therapy for nonsense mutations.
- Goal: Understand individual variants and identify mutation-specific treatment opportunities.
Dr. Julian Halmai — UC Davis (ongoing)
- Area: Gene therapy and stem-cell research
- SMC1A project: Developing a silence-and-replace strategy: suppress endogenous SMC1A and provide a healthy replacement copy.
- Uses patient-derived neural cells, organoids and AAV delivery.
- Goal: Develop a potentially mutation-independent SMC1A gene therapy.
Dr. Xinxian Deng — University of Washington / Seattle Children’s
(ongoing)
- Area: SMC1A disease biology, X-inactivation and gene dosage
- Uses iPSCs, neural progenitors, cortical neurons and organoids.
- SMC1A project: Study how the active versus inactive X chromosome, SMC1A dosage and different variants affect neural cells.
- Goal: Understand why SMC1A variants produce disease in females and what level of SMC1A expression may be therapeutic.
Dr. Katsuhiko Shirahige — University of Tokyo
(ongoing)
- Area: Cohesin biology, genome organization and transcription
- Studies how cohesin regulates DNA organization and gene expression.
- SMC1A relevance: Provides fundamental biology for understanding how altered SMC1A/cohesin function disrupts transcription and cellular function.
Dr. Richard Novak — Unravel Biosciences
(ongoing)
- Area: Computational rare-disease drug discovery
- Uses RNA-seq, pathway/network analysis and computational drug prediction.
- SMC1A project: Analyze patient RNA to identify abnormal pathways and predict drugs or compounds that could shift those pathways toward a healthier state.
- Goal: Identify repurposable drugs, small molecules and therapeutic targets for SMC1A.
Corinne Hunnicutt, Vanderbilt University, Bachelor in Neuroscience 2024 (completed)
- Assignment: a Disease Concept Model of the SMC1A DEE. This will include a literature review, the development of a conceptual model/disease concept study, the creation of molecular mechanisms and figures, and also a strategic research plan.
Abhik Banerjee, MD-PhD Student at the University of Southern California
(completed)
- Study aim: Analysis of Phenotypic and Genotypic profile of patients with SMC1A DEE and SMC1A CDLS. Abhik Banerjee is working on writing a clinical article summarizing phenotypic and genotypic information from patients with SMC1A-Developmental Encephalopathy (SMC1A-DEE). Aiming to write a more comprehnsive analysis of response to AEDs.