Enzyme replacement therapy for lysosomal storage diseases
- PMID: 21946346
- DOI: 10.1097/MOP.0b013e32834c20d9
Enzyme replacement therapy for lysosomal storage diseases
Abstract
Purpose of review: Enzyme replacement therapy (ERT) for type 1 Gaucher has been highly successful. ERT is now available for other lysosomal storage disorders (LSDs) but none of these highly expensive treatments has had the same efficacy. This review explores why these newer treatments have failed to live up to expectations and how future products might be made more effective.
Recent findings: In Gaucher, the target cells for ERT are macrophages, which are efficiently accessed by intravenously injected recombinant enzyme. The target tissues in other LSDs receive much lower doses of enzyme and intravenous ERT does not enter the brain at all. Uptake of recombinant enzyme is via the mannose-6-phosphate receptor (M6PR). Recent work has looked at improving the efficiency of enzyme delivery to tissues by altering both the ligand on the infused enzyme and the expression of the M6PR on cells. For delivery to the central nervous system, intrathecal routes of administration have been explored.
Summary: Work in tissue culture and in animal models has shown increased efficiency of enzyme delivery and clinical trials of second-generation products and novel delivery systems are now underway.
Similar articles
-
Novel treatments and future perspectives: outcomes of intrathecal drug delivery.Int J Clin Pharmacol Ther. 2009;47 Suppl 1:S124-7. Int J Clin Pharmacol Ther. 2009. PMID: 20040323 Review.
-
Enzyme replacement therapy for lysosomal storage diseases.Pediatr Endocrinol Rev. 2012 Oct;10 Suppl 1:26-34. Pediatr Endocrinol Rev. 2012. PMID: 23330243 Review.
-
Targeting macrophages with baculovirus-produced lysosomal enzymes: implications for enzyme replacement therapy of the glycoprotein storage disorder galactosialidosis.FASEB J. 2004 Jun;18(9):971-3. doi: 10.1096/fj.03-0941fje. Epub 2004 Apr 14. FASEB J. 2004. PMID: 15084520
-
Enzyme replacement therapy for lysosomal diseases: lessons from 20 years of experience and remaining challenges.Annu Rev Genomics Hum Genet. 2012;13:307-35. doi: 10.1146/annurev-genom-090711-163739. Annu Rev Genomics Hum Genet. 2012. PMID: 22970722 Review.
-
Treatments for lysosomal storage disorders.Biochem Soc Trans. 2010 Dec;38(6):1465-8. doi: 10.1042/BST0381465. Biochem Soc Trans. 2010. PMID: 21118108
Cited by
-
NEXT STEP IN DRUG DELIVERY: GETTING TO INDIVIDUAL ORGANELLES.Drug Deliv Transl Res. 2012 Dec 1;2(6):415-417. doi: 10.1007/s13346-012-0102-2. Epub 2012 Oct 11. Drug Deliv Transl Res. 2012. PMID: 23565351 Free PMC article. No abstract available.
-
Enzyme replacement therapy attenuates disease progression in a canine model of late-infantile neuronal ceroid lipofuscinosis (CLN2 disease).J Neurosci Res. 2014 Nov;92(11):1591-8. doi: 10.1002/jnr.23423. Epub 2014 Jun 17. J Neurosci Res. 2014. PMID: 24938720 Free PMC article.
-
Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy.Hum Mol Genet. 2013 Apr 15;22(8):1525-38. doi: 10.1093/hmg/ddt003. Epub 2013 Jan 9. Hum Mol Genet. 2013. PMID: 23307925 Free PMC article.
-
Synthesis of high-mannose oligosaccharides containing mannose-6-phosphate residues using regioselective glycosylation.Carbohydr Res. 2018 Sep;467:23-32. doi: 10.1016/j.carres.2018.07.005. Epub 2018 Jul 31. Carbohydr Res. 2018. PMID: 30075362 Free PMC article.
-
Increased Choroidal Thickness in Morquio Syndrome.Case Rep Ophthalmol. 2021 Sep 27;12(3):816-823. doi: 10.1159/000518443. eCollection 2021 Sep-Dec. Case Rep Ophthalmol. 2021. PMID: 34720983 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
