Fibroblast screening for chaperone therapy in beta-galactosidosis

Brain & Development
Hiroyuki IwasakiYoshiyuki Suzuki

Abstract

We performed screening of beta-galactosidase-deficient fibroblasts for possible chemical chaperone therapy using N-octyl-4-epi-beta-valienamine (NOEV) in patients with GM1-gangliosidosis and Morquio B disease (beta-galactosidosis). Fibroblasts were cultured with NOEV for 4 days and beta-galactosidase activity was measured. Mutation analysis was performed simultaneously. Two separate criteria were set for evaluation of the chaperone effect: a relative increase of enzyme activity (more than 3-fold), and an increase up to more than 10% normal enzyme activity. Among the 50 fibroblast strains tested, more than 3-fold increase was achieved in 17 cell strains (34%), and more than 10% normal activity in 10 (20%). Both criteria were satisfied in 6 (12%), and either of them in 21 (42%). Juvenile GM1-gangliosidosis was most responsive, and then infantile GM1-gangliosidosis. This enhancement was mutation-specific. We estimate that the NOEV chaperone therapy will be effective in 20-40% of the patients, mainly in juvenile and infantile GM1-gangliosidosis patients. A molecular design may produce mutation-specific chaperone compounds for the other disease phenotypes. This cellular screening will be useful for identification of human patients w...Continue Reading

References

Jan 1, 1985·Journal of Inherited Metabolic Disease·A Tylki-SzymańskaB Czartoryska
Sep 25, 1995·Biochemical and Biophysical Research Communications·T OkumiyaY Suzuki
Mar 27, 1996·Biochemical and Biophysical Research Communications·S IshiiY Suzuki
Jul 7, 2001·The New England Journal of Medicine·A FrustaciR J Desnick
Jun 18, 2002·Blood Cells, Molecules & Diseases·Rene HeitnerAri Zimran
Dec 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Junichiro MatsudaYoshiyuki Suzuki

❮ Previous
Next ❯

Citations

Feb 1, 2013·Journal of Medicinal Chemistry·Robert E BoydKenneth J Valenzano
Jan 23, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tomoko TakaiYoshiyuki Suzuki
May 27, 2011·Assay and Drug Development Technologies·Kenneth J ValenzanoElfrida R Benjamin
Apr 2, 2009·Pediatrics·Orna Staretz-ChachamEllen Sidransky
Nov 19, 2013·Pharmaceutical Patent Analyst·Juan AymamiMarc Martinell
Sep 13, 2013·Future Medicinal Chemistry·Katsumi HigakiEiji Nanba
Sep 27, 2012·Expert Opinion on Pharmacotherapy·Carin M van GelderArnold J J Reuser
Mar 23, 2012·Molecular Genetics and Metabolism·Yoshiyuki SuzukiKousaku Ohno
Sep 10, 2010·Molecular Genetics and Metabolism·Linjing LiEiji Nanba
Jan 16, 2010·Brain & Development·Zhuo LuanYoshiyuki Suzuki
Oct 28, 2009·Blood Cells, Molecules & Diseases·Zhuo LuanYoshiyuki Suzuki
Nov 13, 2007·Annals of Neurology·Yoshiyuki SuzukiRoscoe O Brady
Oct 10, 2006·Brain & Development·Satoshi IchinomiyaYoshiyuki Suzuki
Jun 26, 2015·Journal of Human Genetics·Mohammad Arif HossainNorio Sakai
Oct 16, 2009·Chembiochem : a European Journal of Chemical Biology·Zhuo LuanYoshiyuki Suzuki
Aug 18, 2010·Chembiochem : a European Journal of Chemical Biology·Georg SchitterTanja M Wrodnigg
Mar 5, 2014·Organic & Biomolecular Chemistry·Julio Rodríguez-LavadoJosé M García Fernández
Dec 20, 2013·Journal of Pediatric Endocrinology & Metabolism : JPEM·Xiaoyun WuYang Ai
Sep 18, 2016·Journal of Neuroscience Research·Adriana Carol Eleonora GrazianoVenera Cardile
Feb 20, 2020·JIMD Reports·Iman S AbumansourSylvia Stockler-Ipsiroglu
Jun 24, 2008·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Anna CaciottiAmelia Morrone
Nov 25, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Arnold E StützTanja M Wrodnigg

❮ 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.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Junichiro MatsudaYoshiyuki Suzuki
Journal of Inherited Metabolic Disease
Yoshiyuki Suzuki
Proceedings of the National Academy of Sciences of the United States of America
Anu R SawkarJeffery W Kelly
© 2022 Meta ULC. All rights reserved