Research

LBSL research is emerging and geographically diverse. Although first discovered in 2004, meaningful studies of the DARS2 gene—which determines LBSL—were not published until 2012. As a result of our efforts, the first comprehensive LBSL research program performing both clinical and scientific studies was launched at the Kennedy Krieger Institute (KKI) at Johns Hopkins University in 2016. Today, we actively support research into LBSL and the DARS2 gene mutation at four universities. Our organization aims to expand this research to new centers of learning and new patient populations around the globe – connecting researchers, clinicians and patient communities with a goal of generating cohesive collaboration, improving patient outcomes, and advancing cures.

Accessing Research Opportunities: A Step-by-Step Guide for the LBSL Community

Cure LBSL is partnering with top researchers around the world to find new treatments, and you can help! 

There are many ways to contribute to research. By connecting with doctors and scientists, sharing your lived experience, and tracking your health and symptoms, you can advance scientific understanding and help drive the development of future treatments and clinical trials.

You may participate in as many studies as you would like. However, we strongly encourage you to please enroll in the LBSL projects first. Industry partners often consult with patient registries to determine how many eligible people might be interested in participating in a clinical trial. When they see strong representation from an active patient group, they are more likely to partner. Let’s make sure they know the global LBSL community is ready for research!

Download "Accessing Research Opportunities: A Step-by-Step Guide for the LBSL Community" to learn more:

  • Step 1: Research Ready

  • Step 2: Patient Registries

  • Step 3: Natural History Studies

  • Step 4: Biorepositories & Human Tissue Studies

  • Step 5: Observational Research Studies

  • Step 6: Interventional Research Studies

  • Step 7: Experimental Treatments / Clinical Trials

  • Step 8: Personalized / Precision Medicine (N=1)

LBSL Research Centers

Kennedy Krieger Institute

Since 2016 the research team at the Moser Center for Leukodystrophies at the Kennedy Krieger Institute in Baltimore, Maryland has made major progress in understanding of the disease process involved in DARS2 gene function and are gearing towards therapeutic targets for LBSL. The team has been working on human observational studies, as well as animal and cell studies testing several therapeutic strategies. The studies utilize wearable technology, neuroimaging, and machine learning methodologies. To summarize, scientists have made several new discoveries and believe that they are on the right path towards identifying therapeutics that they can then push forward towards clinical trials. All thanks to your donations!

Children’s Hospital of Philadelphia

Cure LBSL has joined forces with CureARS to fund a pre-clinical research project with the Mitochondrial Medicine Frontier Program at Children’s Hospital of Philadelphia (CHOP). The aim of this innovative research is to establish and study a full set of animal models for all 19 mitochondrial aminoacyl tRNA synthetase producing genes ("ARS genes" like DARS2 involved in LBSL) and to evaluate potential therapies in these models via high-throughput screening. Drug repurposing involves the study of existing drugs and using them for a medical condition different from what they were originally developed. This strategy offers an expedited and cost saving route to developing new clinical treatments in comparison to traditional drug development. High-throughput screening for this project will examine several thousand already approved FDA drugs and natural product compounds to test their comparative safety and effectiveness.

University of Helsinki

  • New project underway. Information coming soon!

Children's Hospital of Orange County

  • New project underway. Information coming soon!

Hospital Pequeno Príncipe

  • New project underway. Information coming soon!

Select LBSL Publications

Mutations in DARS2 Result in Global Dysregulation of mRNA Metabolism and Splicing

Year: 2023
Authors: Shiqi Guang, Brett M. O'Brien, Amena Smith Fine, Mingyao Ying, Ali Fatemi, Christina L. Nemeth
Journal: Nature - Scientific Reports 
Link: https://pubmed.ncbi.nlm.nih.gov/37563224

Wearable Sensors Detect Impaired Gait and Coordination in LBSL During Remote Assessments

Year: 2022
Authors: Amena Smith Fine, Miriam L. Kaufman , Jordan Goodman, Bela Turk, Amy Bastian, Doris Lin, Ali Fatemi, Jennifer Keller
Journal: Annals of Clinical and Translational Neurology 
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994975

The Leukodystrophies HBSL and LBSL - Correlates and Distinctions

Year: 2020
Authors: Annapoorani Muthiah, Gary D. Housley, Matthias Klugmann, Dominik Fröhlich
Journal: Frontiers in Cellular Neuroscience 
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870476

Mitochondrial Aminoacyl-tRNA Synthetase Disorders: An Emerging Group of Developmental Disorders of Myelination

Year: 2019
Authors: Amena Smith Fine, Christina L. Nemeth, Miriam L. Kaufman , Ali Fatemi 
Journal: Journal of Neurodevelopmental Disorders 
Link: https://rdcu.be/c2Urk

Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation: Clinical and Genetic Characterization and Target for Therapy

Year: 2014
Authors: Laura van Berge,  Eline M Hamilton,  Tarja Linnankivi,  Graziella Uziel,  Marjan E Steenweg,  Pirjo Isohanni,  Nicole I Wolf,  Ingeborg Krägeloh-Mann,  Nils J Brautaset,  P Ian Andrews, Brigit A de Jong,  Malak al Ghamdi,  Wessel N van Wieringen,  Bakhos A Tannous,  Esther Hulleman,  Thomas Würdinger,  Carola G M van Berkel,  Emiel Polder,  Truus E M Abbink,  Eduard A Struys,  Gert C Scheper,  Marjo S van der Knaap, LBSL Research Group
Journal: Brain
Link: https://academic.oup.com/brain/article/137/4/1019/369983

A New Leukoencephalopathy with Brainstem and Spinal Cord Involvement and High Lactate

Year: 2003
Authors: Marjo S. Van Der Knaap MD, PhD,  Patrick Van Der Voorn MD,  Frederik Barkhof MD, PhD,  Rudy Van Coster MD, PhD,  Ingeborg Krägeloh-Mann MD,  Annette Feigenbaum MD,  Susan Blaser MD,  Johan S. H. Vles MD, PhD,  Peter Rieckmann MD,  Petra J. W. Pouwels PhD
Journal: Annals of Neurology 
Link: https://onlinelibrary.wiley.com/doi/10.1002/ana.10456