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Pharmacological chaperone therapy for Gaucher disease: A patent review
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2011
- Publisher :
- Ashley Publications, 2011.
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Abstract
- Introduction: Mutations in the gene encoding for acid β-glucosidase (β-glucocerebrosidase, GlcCerase) are seen in Gaucher disease (GD), which give rise to significant protein misfolding effects and result in progressive accumulation of glucosyl ceramide. The main treatment for GD is enzyme replacement therapy (ERT). The iminosugar glycosidase inhibitor N-(n-butyl)-1-deoxynojirimycin (miglustat, Zavesca™) is used in a second treatment modality known as substrate reduction therapy. At the beginning of the 21st century, a third therapeutic paradigm was launched, namely, pharmacological chaperone therapy (PCT). This therapeutic strategy relies on the capability of such inhibitors to promote the correct folding and stabilize mutant forms of lysosomal enzymes, such as GlcCerase, as they pass through the secretory pathway. Areas covered: This review summarizes the different approaches used to implement the concept of PCT for GD. It discusses the relevant research, patents and patent applications filed in the last decade. Expert opinion: While the significance of PCT remains a matter of debate, the great interest gathered regarding it in a relatively few years reflects its broad potential scope, well beyond GD. The fact that pharmacological chaperones can be designed to cross the blood brain barrier (BBB) make them candidates for the treatment of neuronopathic forms of GD that are not responsive to ERT. Combined therapies offer even broader possibilities that deserve to be fully explored. © 2011 Informa UK, Ltd.<br />The authors thank the the Spanish Ministerio de Ciencia e Innovación (contract numbers CTQ2007-61180/PPQ and SAF2010-84015670), the Fundación Ramón Areces, the Junta de Andalucía (Project P08-FQM-03711) and the European Union for sustained financial support in the field covered by this review.
- Subjects :
- Glucocerebrosidase
Protein Folding
Pharmacological chaperone therapy
Iminosugar
Drug Evaluation, Preclinical
Gaucher disease
Pharmacology
Biology
Iminosugars
lysosomal storage disorders
Patents as Topic
Miglustat
Drug Discovery
medicine
Humans
Substrate reduction therapy
Enzyme Replacement Therapy
Gaucher Disease
Nojirimycin
Glycosidase inhibitors
Folding diseases
General Medicine
Enzyme replacement therapy
Isofagomine
Pharmacological chaperone
Ambroxol
Chemical chaperones
Blood-Brain Barrier
Drug Design
Immunology
Chemical chaperone
medicine.drug
Imino Pyranoses
Molecular Chaperones
Subjects
Details
- ISSN :
- 20076118
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....4b2f77c3c8d5b7312310ad01cb2824b9