Newly discovered leukodystrophy in children: Potential cure
The gene that causes the disease is called DEGS1 and its defect may be counteracted with fingolimod
- Date:
- January 10, 2019
- Source:
- IDIBELL-Bellvitge Biomedical Research Institute
- Summary:
- Medical researchers have uncovered a novel disease of children affecting the brain white matter -- the myelin sheath --, leading to severe incapacity and death in some cases. These defects were corrected by a treatment with fingolimod, a drug in use for multiple sclerosis which interferes with this pathway.
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The Neurometabolic Diseases research team at IDIBELL and CIBER of Rare Diseases (CIBERER), led by ICREA Professor Aurora Pujol, has uncovered a novel disease of children affecting the brain white matter -the myelin sheath-, leading to severe incapacity and death in some cases.
The gene causing the disorder is called DEGS1 and was identified using whole exome sequencing (WES) of 19 patients from around the globe (China, Iran, Morocco, USA, and France). "Sample collection for such a rare disease was extremely fast thanks to our collaboration with reference centers for leukodystrophies in France (Dr Odile Boespflug-Tanguy) and in Baltimore (Dr Ali Fatemi), and to the freely accessible genomic information exchange platform GeneMatcher," Dr Pujol explains.
DEGS1 is an enzyme of lipid metabolism that converts dihydroceramides to ceramides, at a hub essential for brain function. Indeed, defects in other enzymes along this pathway cause similar rare diseases like Krabbe disease or Metachromatic Leukodystrophy, also affecting the myelin..
A zebrafish model with deficient DEGS1 function was generated in the laboratory of Dr Cristina Pujades, UPF Barcelona, and exhibited swimming difficulties, loss of myelin forming cells (oligodendrocytes) and ceramide imbalances. These defects were corrected by a treatment with fingolimod, a drug in use for multiple sclerosis which interferes with this pathway. "These results pave the way to clinical trials, illustrating the transformative impact of clinical and functional genomics in the continuum from diagnostics to treatment," adds Dr Pujol.
Story Source:
Materials provided by IDIBELL-Bellvitge Biomedical Research Institute. Note: Content may be edited for style and length.
Journal Reference:
- Devesh C. Pant, Imen Dorboz, Agatha Schlüter, Stéphane Fourcade, Nathalie Launay, Javier Joya, Sergio Aguilera-Albesa, Maria Eugenia Yoldi, Carlos Casasnovas, Mary J. Willis, Montserrat Ruiz, Dorothée Ville, Gaetan Lesca, Karine Siquier-Pernet, Isabelle Desguerre, Huifang Yan, Jinming Wang, Margit Burmeister, Lauren Brady, Mark Tarnopolsky, Carles Cornet, Davide Rubbini, Javier Terriente, Kiely N. James, Damir Musaev, Maha S. Zaki, Marc C. Patterson, Brendan C. Lanpher, Eric W. Klee, Filippo Pinto e Vairo, Elizabeth Wohler, Nara Lygia de M. Sobreira, Julie S. Cohen, Reza Maroofian, Hamid Galehdari, Neda Mazaheri, Gholamreza Shariati, Laurence Colleaux, Diana Rodriguez, Joseph G. Gleeson, Cristina Pujades, Ali Fatemi, Odile Boespflug-Tanguy, Aurora Pujol. Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. Journal of Clinical Investigation, 2019; DOI: 10.1172/JCI123959
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