22 août 2009
Production de l'enzyme recombinant GCD exprimé dans des cellules de carrots
Vous trouverez des articles traitant du même sujet dans la catégorie "A propos des essais thérapeutiques". Ghislaine SURREL maladies-lysosomales-subscribe@yahoogroupes.f
Plant Biotechnol J. 2007 Sep;5(5):579-90. Epub 2007 May 24.
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Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system.
Shaaltiel Y, Bartfeld D, Hashmueli S, Baum G, Brill-Almon E, Galili G, Dym O, Boldin-Adamsky SA, Silman I, Sussman JL, Futerman AH, Aviezer D.
Protalix Biotherapeutics, 2 Snunit Street, Science Park, Carmiel 20100, Israel.Gaucher's disease, a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy using recombinant GCD (Cerezyme) expressed in Chinese hamster ovary (CHO) cells. As complex glycans in mammalian cells do not terminate in mannose residues, which are essential for the biological uptake of GCD via macrophage mannose receptors in human patients with Gaucher's disease, an in vitro glycan modification is required in order to expose the mannose residues on the glycans of Cerezyme. In this report, the production of a recombinant human GCD in a carrot cell suspension culture is described. The recombinant plant-derived GCD (prGCD) is targeted to the storage vacuoles, using a plant-specific C-terminal sorting signal. Notably, the recombinant human GCD expressed in the carrot cells naturally contains terminal mannose residues on its complex glycans, apparently as a result of the activity of a special vacuolar enzyme that modifies complex glycans. Hence, the plant-produced recombinant human GCD does not require exposure of mannose residues in vitro, which is a requirement for the production of Cerezyme. prGCD also displays a level of biological activity similar to that of Cerezyme produced in CHO cells, as well as a highly homologous high-resolution three-dimensional structure, determined by X-ray crystallography. A single-dose toxicity study with prGCD in mice demonstrated the absence of treatment-related adverse reactions or clinical findings, indicating the potential safety of prGCD. prGCD is currently undergoing clinical studies, and may offer a new and alternative therapeutic option for Gaucher's disease.
Publication Types:
PMID: 17524049 [PubMed - indexed for MEDLINE]
19 août 2009
Lettre de Genzyme du 3/08/09 aux US malades : révision du programme de gestion du stock
Vous trouverez des articles traitant du même sujet dans la catégorie "A propos des traitements et prise en charge". Liens utiles à la fin des catégories. maladies-lysosomales-subscribe@yahoogroupes.fr Genzyme Corporation 500 Kendall Street Cambridge, MA 02142 Tel 617-252-7500 August 4, 2009 RE: Revised Cerezyme® (imiglucerase for injection) Supply Management plan effective August 3, 2009 Dear Patient: I am writing to you today to provide an important update on the period of temporary shortage of Cerezyme. We continue to work diligently to restore production at our Allston facility and to responsibly manage the supply of Cerezyme with the goal of protecting the most vulnerable patients. We realize that this situation presents very real challenges for patients, their families, and their physicians during this time. We are so grateful for the many efforts made by members of the Gaucher community to conserve supply either by missing or reducing doses, as those efforts have helped with supply conservation. However, although many physicians and patients have communicated their intent to alter their treatment regimens there has not yet been a significant reduction in the amount of Cerezyme orders and shipments. Currently, our levels of inventory of Cerezyme on hand are at a point that we are at risk of not maintaining enough product to enable the most vulnerable patients to continue receiving their regular doses through the entire period of supply constraint. On Friday, July 31, the Cerezyme Stakeholders Working Group (composed of patient advocacy leaders, and fourteen U.S. physicians) met to review the current situation and as well as a revised supply management plan for the month of August. In order to preserve inventory for the most vulnerable patients, effective immediately we will only ship Cerezyme for Gaucher patients who fall into the following three groups: children 18 years of age and younger, patients with neuronopathic Gaucher (type 2 and type 3), and those patients facing life-threatening clinical situations. A Cerezyme Emergency Access Program (CEAP) has been established to allow patients and physicians to apply for emergency access in the case of life-threatening need. The Cerezyme Stakeholders Working Group will reassess inventories at the end of August 2009 and help to determine the best way forward. Please speak with your doctor about this updated plan and for more information. Should you have questions, you may also call your Genzyme Case Manager or Genzyme Medical Information at 1-800-745-4447. A copy of the Cerezyme US Prescribing Information is included with this letter. This information does not take the place of talking to your doctor about your condition or your treatment. Please be assured that Genzyme is resolute in our commitment to patients, and continues to work to support Gaucher families in the US and around the world We are steadfast in our determination to work collaboratively with the FDA, the Gaucher patient community, and physicians to best manage these challenges. Sincerely, C. Geoffrey McDonough, MD Senior Vice President, General Manager Lysosomal Storage Disorders Therapeutics CZ-US-P073-08-09
Ghislaine SURREL
26 juin 2007
AT2101 (Amicus Therapeutics) /Orphan status for Gaucher disease drug
Vous trouverez des articles traitant du même sujet dans la catégorie "A propos des essais thérapeutiques"
Liens utiles à la fin des catégories.
Ghislaine SURREL
maladies-lysosomales-subscribe@yahoogroupes
In February 2006 the U.S. Food and Drug Administration (FDA) approved orphan drug status for AT2101 (Amicus Therapeutics) for the treatment of Gaucher disease, a lysosomal storage disorder resulting from deficiency of the enzyme glucocerebrosidase. AT2101 is an oral drug which helps restore the proper structure and cellular movement of glucocerebrosidase. Clinical studies of the drug are expected to begin during the first half of 2006.
Amicus Therapeutics is also conducting Phase II clinical trials for the drug AT1001 (migalastat hydrochloride) for treatment of another storage disorder, Fabry disease.
Friday March 10, 2006
http://rarediseases.about.com/b/a/250787.htm?terms=GAUCHER
