Pharmacological chaperone therapy for Gaucher disease: A patent review
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 replaceme...
| Authors: | ; ; |
|---|---|
| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2011 |
| Country: | España |
| Institution: | Universidad de Sevilla (US) |
| Repository: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/139401 |
| Online Access: | https://hdl.handle.net/11441/139401 https://doi.org/10.1517/13543776.2011.569162 |
| Access Level: | Open access |
| Keyword: | Ambroxol Chemical chaperones Folding diseases Gaucher disease Glucocerebrosidase Glycosidase inhibitors Iminosugars Isofagomine lysosomal storage disorders Nojirimycin Pharmacological chaperone therapy |
| _version_ | 1878740723484852224 |
|---|---|
| author | Benito, Juan Manuel |
| author2 | García Fernández, José Manuel Ortiz Mellet, Carmen |
| author2_role | author author |
| author_browse | Benito, Juan Manuel García Fernández, José Manuel Ortiz Mellet, Carmen |
| author_facet | Benito, Juan Manuel García Fernández, José Manuel Ortiz Mellet, Carmen |
| author_role | author |
| collection | idUS. Depósito de Investigación de la Universidad de Sevilla |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_d83ade6e2e0828e1f0f1fa58471b2b86 |
| institution | Universidad de Sevilla (US) |
| instname_str | Universidad de Sevilla (US) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:idus.us.es:11441/139401 |
| publishDate | 2011 |
| publishDateSort | 2011 |
| publisher | Taylor & Francis |
| publisherStr | Taylor & Francis |
| reponame_str | idUS. Depósito de Investigación de la Universidad de Sevilla |
| spelling | Pharmacological chaperone therapy for Gaucher disease: A patent review Benito, Juan Manuel García Fernández, José Manuel Ortiz Mellet, Carmen Ambroxol Chemical chaperones Folding diseases Gaucher disease Glucocerebrosidase Glycosidase inhibitors Iminosugars Isofagomine lysosomal storage disorders Nojirimycin Pharmacological chaperone therapy 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. Ministerio de Ciencia e Innovación CTQ2007-61180/PPQ, SAF2010-15670 Junta de Andalucía P08-FQM-03711 Taylor & Francis https://hdl.handle.net/11441/139401 https://doi.org/10.1517/13543776.2011.569162 |
| spellingShingle | Pharmacological chaperone therapy for Gaucher disease: A patent review Benito, Juan Manuel Ambroxol Chemical chaperones Folding diseases Gaucher disease Glucocerebrosidase Glycosidase inhibitors Iminosugars Isofagomine lysosomal storage disorders Nojirimycin Pharmacological chaperone therapy |
| status_str | acceptedVersion |
| title | Pharmacological chaperone therapy for Gaucher disease: A patent review |
| title_full | Pharmacological chaperone therapy for Gaucher disease: A patent review |
| title_fullStr | Pharmacological chaperone therapy for Gaucher disease: A patent review |
| title_full_unstemmed | Pharmacological chaperone therapy for Gaucher disease: A patent review |
| title_short | Pharmacological chaperone therapy for Gaucher disease: A patent review |
| title_sort | Pharmacological chaperone therapy for Gaucher disease: A patent review |
| topic | Ambroxol Chemical chaperones Folding diseases Gaucher disease Glucocerebrosidase Glycosidase inhibitors Iminosugars Isofagomine lysosomal storage disorders Nojirimycin Pharmacological chaperone therapy |
| topic_facet | Ambroxol Chemical chaperones Folding diseases Gaucher disease Glucocerebrosidase Glycosidase inhibitors Iminosugars Isofagomine lysosomal storage disorders Nojirimycin Pharmacological chaperone therapy |
| url | https://hdl.handle.net/11441/139401 https://doi.org/10.1517/13543776.2011.569162 |