Cytidine Diphosphate-Ribitol Analysis for Diagnostics and Treatment Monitoring of Cytidine Diphosphate-l-Ribitol Pyrophosphorylase A Muscular Dystrophy

Clinical Chemistry
Walinka van TolDirk J Lefeber

Abstract

Many muscular dystrophies currently remain untreatable. Recently, dietary ribitol has been suggested as a treatment for cytidine diphosphate (CDP)-l-ribitol pyrophosphorylase A (CRPPA, ISPD), fukutin (FKTN), and fukutin-related protein (FKRP) myopathy, by raising CDP-ribitol concentrations. Thus, to facilitate fast diagnosis, treatment development, and treatment monitoring, sensitive detection of CDP-ribitol is required. An LC-MS method was optimized for CDP-ribitol in human and mice cells and tissues. CDP-ribitol, the product of CRPPA, was detected in all major human and mouse tissues. Moreover, CDP-ribitol concentrations were reduced in fibroblasts and skeletal muscle biopsies from patients with CRPPA myopathy, showing that CDP-ribitol could serve as a diagnostic marker to identify patients with CRPPA with severe Walker-Warburg syndrome and mild limb-girdle muscular dystrophy (LGMD) phenotypes. A screen for potentially therapeutic monosaccharides revealed that ribose, in addition to ribitol, restored CDP-ribitol concentrations and the associated O-glycosylation defect of α-dystroglycan. As the effect occurred in a mutation-dependent manner, we established a CDP-ribitol blood test to facilitate diagnosis and predict individual...Continue Reading

References

Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·A Y LeeS S Chung
Aug 1, 1993·The Journal of Cell Biology·J M Ervasti, K P Campbell
May 1, 1958·The Journal of Clinical Investigation·S SEGAL, J FOLEY
Apr 15, 2004·Medical Hypotheses·Stephen L DoddJohn A St Cyr
Jul 6, 2004·Molecular Genetics and Metabolism·Jojanneke H J HuckNanda M Verhoeven
Sep 26, 2007·American Heart Journal·Lizzy M BrewsterGert A van Montfrans
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Aug 3, 2010·Nature Methods·Jana Marie SchwarzDominik Seelow
Oct 15, 2010·Kidney International·Kenichiro KojimaShunya Uchida
Nov 17, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sebahattin CirakFrancesco Muntoni
Mar 8, 2013·Lancet·Eugenio Mercuri, Francesco Muntoni
Aug 3, 2013·Annals of Neurology·Jerry R MendellUNKNOWN Eteplirsen Study Group
Sep 13, 2013·Annual Review of Microbiology·Stephanie BrownSuzanne Walker
Feb 7, 2014·The New England Journal of Medicine·Laura C TegtmeyerThorsten Marquardt
Mar 20, 2015·Journal of the American College of Nutrition·Stephen T Sinatra, Corby Caiazzo
Nov 18, 2015·Annals of Neurology·Jerry R MendellUNKNOWN Eteplirsen Study Group and Telethon Foundation DMD Italian Network
Dec 22, 2015·Chemistry & Biology·Moniek RiemersmaDirk J Lefeber
May 10, 2017·Molecular Therapy. Methods & Clinical Development·Charles Harvey VannoyQi Long Lu
Nov 8, 2017·Nutrients·Peter WittersEva Morava

❮ Previous
Next ❯

Citations

May 23, 2020·Journal of Inherited Metabolic Disease·Minela HaskovicM Estela Rubio-Gozalbo

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.